A Pilot Plant-Based Dietary Intervention in Overweight and Obese Patients With Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) - The Nutrition Prevention (NUTRIVENTION) Study
Phase: NA
Conditions: Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-135 A(6) 
Approval date: 27-Mar-2024 
 
 
MSK PROTOCOL COVER SHEET 
A Pilot Plant-Based Dietary Intervention in Overweight and Obese Patients with Monoclonal 
Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) - 
The Nutrition Prevention (NUTRIVENTION) Study 
 
 
 
Principal Investigator/Department: 
Urvi Shah, MD / Medicine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 1 of 45 

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IRB Number: 21-135 A(6) 
Approval date: 27-Mar-2024 
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Page 2 of 45 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ......................................................................... 3 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS .................................................................................. 5 
3.0 
BACKGROUND AND RATIONALE ........................................................................................ 6 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION............................................................... 15 
4.1 
Design ............................................................................................................................... 15 
4.2 
Intervention ........................................................................................................................ 15 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS ............ 16 
6.0 
CRITERIA FOR PARTICIPANT ELIGIBILITY ....................................................................... 16 
6.1 
Participant Inclusion Criteria .............................................................................................. 16 
6.2 
Participant Exclusion Criteria ............................................................................................. 17 
7.0 
RECRUITMENT PLAN ......................................................................................................... 17 
7.1 
Research Participant Registration ...................................................................................... 17 
7.2 
Randomization................................................................................................................... 18 
7.3 
Accrual .............................................................................................................................. 18 
8.0 
INFORMED CONSENT PROCEDURES ................................................................................ 18 
9.0 
PRE-TREATMENT/INTERVENTION ..................................................................................... 19 
10.0 TREATMENT/INTERVENTION PLAN .................................................................................. 20 
11.0 EVALUATION DURING TREATMENT/INTERVENTION ...................................................... 22 
12.0 CRITERIA FOR REMOVAL FROM STUDY .......................................................................... 27 
13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY .................. 27 
14.0 BIOSTATISTICS ................................................................................................................... 32 
15.0 TOXICITIES/RISKS/SIDE EFFECTS .................................................................................... 34 
15.1 Serious Adverse Event (SAE) Reporting ............................................................................ 34 
16.0 PROTECTION OF HUMAN PARTICIPANTS ........................................................................ 35 
16.1 Privacy .............................................................................................................................. 37 
16.2 Data Management ............................................................................................................... 38 
16.4 Quality Assurance ............................................................................................................. 38 
16.5 Data and Safety Monitoring ............................................................................................... 39 
17.0 
REFERENCES ..................................................................................................................... 40 
18.0 
APPENDICES ...................................................................................................................... 44 

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IRB Number: 21-135 A(6) 
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1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
Study title: A pilot plant-based dietary intervention in overweight and obese patients with 
monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple 
myeloma (SMM). 
Rationale: 
Multiple myeloma (MM) is a plasma cell neoplasm often preceded by the premalignant 
conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering 
multiple myeloma (SMM). Obesity, low adiponectin levels, and diets high in insulinemic foods 
or lacking plant-based foods are known risk factors for the development of MGUS/SMM, as 
well as for progression to MM. Therefore, there is an opportunity to study a dietary 
intervention in cancer progression among patients with MGUS/SMM, for which the standard 
of care is observation even though many patients will eventually progress to MM. We plan to 
conduct a pilot nutrition-based intervention study of a whole food, plant-based diet (WFPBD) 
in overweight and obese MGUS/SMM patients to enable weight loss, as well as to assess 
associated changes in biomarkers of disease, epigenetics, and the gut microbiome. We 
expect that the findings will enable larger lifestyle-based studies of prevention and 
survivorship in plasma cell disorders. 
Objectives: 
Primary – 
To determine the feasibility of a WFPBD in obese/overweight patients with MGUS or SMM, 
as measured by weight loss and adherence at 12 weeks. 
Secondary – 
1. To determine the feasibility of a WFPBD in obese/overweight patients with MGUS or 
SMM, as measured by safety, and quality of life. 
2. To assess weight loss at 24, or 52 weeks. 
3. To assess alterations in metabolic, and myeloma markers secondary to a WFPBD 
intervention. 
Exploratory – 
1. To assess alterations in T cell and plasma cell epigenetic markers secondary to a 
WFPBD intervention. 
2. To assess alterations in the fecal microbiome after a WFPBD intervention. 
3. To assess changes in immune function after a WFPBD intervention. 
4. To assess changes in body composition (visceral, subcutaneous and bone marrow 
fat) as determined on PET imaging and correlate with weight changes as well as 
markers of disease. 

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Patient population: Eligible patients will have either SMM or MGUS and be older than 18 
years with BMI ≥25, M spike (immunoglobulin) ≥0.2 g/dL or abnormal free light chain ratio, 
ECOG performance status 0-3, and willingness to comply with study-related procedures. 
Design: This is a single-arm, single-center pilot study with 20 patients. 
Treatment plan: For 12 weeks, patients will receive two premade meals per day, for lunch 
and dinner for 6 days weekly, prepared and shipped by U.S.-based WFPBD company 
Plantable weekly. The meals will have a low glycemic index and contain vegetables, whole 
grains, and plant-based fats that have undergone minimal processing. Detailed 
recommendations for snacks and breakfasts meeting the standard of a WFPBD will also be 
given to supplement their daily calorie needs with access to an online portal from Plantable 
which contains education materials and access to a coach daily. Patients will also receive 
dietary education and counselling from a research dietitian every 2 weeks for the 12 week 
intervention period. They will have access to the team for questions and support as needed. 
Upon joining the trial, patients will receive vitamin repletion of folate, iron, vitamin B12, and 
vitamin D to within the normal range if necessary. 
Enrollment: We anticipate enrollment of about 2 patients per month and therefore a total 
enrollment time of about 10 months. 
Figure 1: Schema 

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IRB Number: 21-135 A(6) 
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2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
This study aims to test the hypothesis that a WFPBD will be associated with weight loss and 
will alter metabolic markers and the microbiome (Figure 2) in ways which may reduce the 
risk of progression from MGUS and SMM to MM. This hypothesis will be tested in a pilot 
clinical study of 20 patients, who will receive a WFPBD intervention for 12 weeks. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-135 A(6) 
Approval date: 27-Mar-2024 
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Primary objective 
To determine the feasibility of a WFPBD in obese/overweight patients with MGUS or SMM, 
as measured by weight loss and adherence at 12 weeks. 
Secondary objectives 
1. To determine the feasibility of a WFPBD in obese/overweight patients with MGUS or 
SMM, as measured by safety, and quality of life. 
2. To assess weight loss at 24, or 52 weeks. 
3. To assess alterations in metabolic, and myeloma markers secondary to a WFPBD 
intervention. 
 
Exploratory objectives 
1. To assess alterations in T cell and plasma cell epigenetic markers secondary to a 
WFPBD intervention. 
2. To assess alterations in the fecal microbiome after a WFPBD intervention. 
3. To assess changes in body composition (visceral, subcutaneous and bone marrow fat) 
as determined on PET imaging and correlate with weight change as well as markers of 
disease. 
 
3.0 
BACKGROUND AND RATIONALE 
Multiple myeloma (MM), the second most common hematologic malignancy, remains 
incurable despite many therapies, approved in the last decade, which improve survival. The 
precursor states of MM—monoclonal gammopathy of undetermined significance (MGUS) 
and smoldering multiple myeloma (SMM)—have a prevalence of ≥3% in adults over the age 
Figure 2: Endpoints and Expected outcomes of a WFPBD in MGUS and SMM. 

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IRB Number: 21-135 A(6) 
Approval date: 27-Mar-2024 
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Page 7 of 45 
 
 
of 50.1 These disorders present opportunities for early intervention to prevent disease 
progression, given that the current standard of care is observation.2 
Common questions among patients with multiple myeloma and its precursor conditions are 
whether diet or lifestyle caused the condition and whether they should alter their food habits. 
Currently, the only data available to guide physicians’ answers is epidemiologic. 
Links between metabolic disorders and MM: In the U.S., over 70% of the population has a 
body mass index (BMI) above normal, and about 45% of adults are prediabetic or diabetic.3,4 
The incidence of obesity-related cancers, including multiple myeloma (MM), is increasing in 
young adults.5 Lifestyle and metabolic disorders are known risk factors for the pathogenesis 
of MM and its precursor disorders,6,7 particularly obesity (odds ratios [OR] 1.80 [95% CI 1.03- 
3.1] and OR 1.50 [95% CI 1.2-2.0], respectively),8-10 low total adiponectin levels (OR 0.49 
[95% CI 0.26-0.93])11, and diabetes (hazard ratio [HR] 1.80 [95% CI 1.52-2.14]).12 Obesity 
has also been shown to increase the risk of progression from MGUS to MM in two studies 
(HR 1.98 [95% CI 1.47-2.68] and HR 2.66 [95% CI 1.17-6.05], respectively).13,14 
Consistent with these studies, a meta analyses of 8 IMMC case-control studies found that 
overweight or obese patients at time of study enrollment had a higher risk for MM (10% 
increased risk for overweight and obese patients whereas 40% increased risk for severely 
obese patients) compared to those with a usual adult BMI. Patients with elevated BMI at two 
time points (study entry as well as at young adult age (ages 25-30 years)) had a significantly 
elevated risk of MM compared with individuals with normal BMI on both measures (p 
<0.0001).15 
However, there have been very limited studies of lifestyle and dietary interventions to prevent 
the development or recurrence of MM.16 
Links between dietary factors and MM: Evidence suggests that inflammation and 
endogenous growth factors, including insulin-like growth factors (IGF)-1 and interleukin (IL)- 
6, play an important role in MM pathogenesis. Diets that are likely to increase inflammation 
and insulin secretion are considered inflammatory and insulinemic dietary patterns. Some 
examples in the literature include the empirical dietary inflammatory pattern (EDIP), empirical 
dietary index for insulin resistance (EDIR) and empirical dietary index for hyperinsulinemia 
(EDIH) and the western diet. Furthermore, such unhealthy dietary patterns have been linked 
to the development of MM.17,18 while vegetarians and vegans have a reduced risk (relative 
risk [RR] 0.23 [95% CI 0.09-0.59]).19 Specifically, fruit-rich diets (>3 times per week; OR 0.62 
[95% CI 0.41-0.95]),20 vegetables-rich diets (4-7 times per week; OR 0.40 [95% CI 0.1- 
1.0]),21 diets high in cruciferous vegetables (>2 times per week [OR 0.50; 95% CI 0.3-0.8]),22 
and diets high in whole grains and thus fiber (>3 days per week; OR 0.50 [95% CI 0.2-1.1])23 
have been associated with a reduced risk of plasma cell disorders. Similarly, fruit intake at 
least three times per week during later life (> 50 years) was associated with a decreased risk 
of progression from MGUS to MM (HR 0.34 [95% CI 0.13-0.89]).20 

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IRB Number: 21-135 A(6) 
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Table 1: 
 
Metabolic 
and Dietary 
Factors 
Risk for 
N 
Risk 
95% CI 
Reference 
Obesity 
MGUS 
1196 (60) 
OR 1.80 
1.03-3.14 
Landgren 
Blood 20108 
Obesity (BMI 
35+) 
MM mortality 
1,564,218 
HR 1.52 
1.15-2.02 
Teras BJH 
201510 
Obesity (BMI 
35+) 
MM 
9609 
controls; 
2318 MM 
OR 1.40 
1.1-1.7 
Birmann 
CEBP 
201715 
Obesity 
MGUS → MM 
7878 MGUS 
HR 1.98 
1.47-2.68 
Chang JNCI 
201713 
Obesity 
MGUS → MM 
575 MGUS 
18 MM & 
11 LPD 
HR 2.66 
1.17-6.05 
Thordardottir 
Blood Adv 
201714 
Adiponectin 
elevation 
MM 
348 controls 
174 MM 
OR 0.49 
0.26-0.93 
Hofmann 
Blood 
201211 
Adiponectin 
elevation 
MM 
624 MM; 
1246 
controls 
OR 0.64 
0.47-0.85 
Hofmann 
Can Res 
20167 
Diabetes 
mellitus 
MM 
2.3 million 
(2134 MM) 
HR 1.80 (M) 
HR 1.58 (F) 
1.52-2.14 
1.30-1.92 
Dankner 
AJE 201512 
Diabetes 
mellitus 
MGUS 
14,048 
MGUS; 
53,072 
controls 
OR 1.58 
1.48-1.68 
(Shah et al, 
submitted to 
ASH 2020) 
Diabetes 
mellitus 
MM 
1,266 MM; 
3,881 
controls 
OR 1.30 
1.22-1.39 
(Shah et al, 
submitted to 
ASH 2020) 
Inflammatory/ 
insulinemic 
potential diets 
MM in males 
116,983 
(478 MM) 
HR 1.16 
1.02-1.32 
Lee JNCI 
Can Spec 
201917 
Unhealthy 
Western dietary 
pattern 
MM mortality 
165796 
(423 MM, 
345 deaths) 
HR 1.24 
1.07-1.44 
Lee IJC 
202018 
Healthy (AHEI- 
2010) dietary 
pattern 
MM mortality 
165796 
(423 MM, 
345 deaths) 
HR 0.76 
0.67-0.87 
Lee IJC 
202018 
Vegetarians/ 
vegans 
MM 
61,647 (65 
MM) 
RR 0.23 
0.09-0.59 
Key AJCN 
201419 
Fruits (>3 times 
per week) 
MGUS 
5,764 (575 
MGUS) 
OR 0.62 
0.41-0.95 
Thordardottir 
Plos One 
201820 

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Fruit intake (>3 
times/week; 
after 50 years) 
MGUS → MM 
5,764 (575 
MGUS) 
HR 0.34 
0.13-0.89 
Thordardottir 
Plos One 
201820 
Vegetables-rich 
diets (4-7 
times/week) 
MM 
100 controls 
100 MM 
OR 0.40 
0.1-1.0 
Vlajinac 
Neoplasma 
200321 
Cruciferous 
vegetables >2 
times/week) 
MM 
670 
controls; 
173 MM 
OR 0.50 
0.3-0.8 
Hosgood 
CCC 200722 
Whole grains 
(>3 days/week) 
MM 
7990 
controls 
120 MM 
OR 0.50 
0.2-1.1 
Chatenoud 
Int J Cancer 
199823 
 
Link between plant based diets, weight loss and reduced cancer risk: Several trials have 
demonstrated the efficacy of vegetarian diets for weight loss and improvement of 
cardiovascular biomarkers – benefits that are thought to be mediated by energy restriction 
and plant constituents (e.g., fiber)24,25. Observational data suggest that vegetarian diets are 
protective against cancer growth and are associated with reduced all-cause mortality26,27. 
One of the largest randomized trials (BROAD study) testing a non-energy restricted whole 
food plant-based diet intervention for 3 months in 65 obese and overweight adults with 
comorbidities showed that there was greater reduction in mean BMI 4.4 kg/m2 vs 0.4 kg/m2 
(p <0.0001) at 6 months which was sustained at 12 months although the study intervention 
ended at 3 months. This dietary intervention achieved greater sustained weight loss than any 
other trial that does not limit energy intake or mandate regular exercise28. Patients on this 
study had regular nutritional counselling and no meals were provided. Given this data of the 
importance and success of nutrition counselling, this study will incorporate nutrition 
counselling for 24 weeks along with the dietary intervention for 12 weeks. (Table 2) 
Plant based dietary approaches led to improvement in the dietary inflammatory index scores 
among overweight and obese adults during a 6 month randomized controlled trial29. Several 
trials have demonstrated that dietary modification after a cancer diagnosis is safe and 
feasible. Most studies to date have been done in solid tumors such as breast cancer30-32, 
prostate cancer33-35, ovarian cancer36 and colon cancer37 as well as cancer survivors35. 
Therefore, plant based diets are feasible for achieving sustainable weight loss in overweight 
and obese patients. Plant-based foods lead to sustained weight loss without calorie 
restriction as they are high in fiber (and are nutrient dense but not calorie dense), which 
helps with early satiety compared to other approaches that are calorie restricted and thus 
unsustainable. Thus, this study will evaluate the combined effects of plant-based nutrients 
(fruits, vegetables, whole grains, beans, legumes) and weight loss that have been shown to 
be associated with reduced risk of MM. 

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Table 2: 
 
 
 
Role of adiponectin in the etiology of obesity related MM: Adiponectin, an adipocyte-specific 
protein that is decreased with obesity and MM, exhibits insulin-sensitizing, anti-inflammatory, 
antiatherogenic, proapoptotic, and antiproliferative properties.38 Prior studies have shown 
that weight loss leads to an increase in adiponectin levels.39 Patients with MGUS who have 
lower adiponectin levels are more likely to progress to MM, and adiponectin induces 
myeloma cell apoptosis in preclinical models.6,40 Patients with SMM and MM also have 
significantly lower adiponectin levels compared to those with MGUS.6 
Decreased serum adiponectin concentrations were seen in MGUS patients who 
subsequently progressed to MM - MGUS with progression 4.5 ug/mL, MGUS with no 
progression 6.4 ug/mL and controls 5.6 ug/mL 40. In another study, adiponectin levels were 
measured in 213 patients at different stages MGUS, SMM, or MM. They found that relative to 
MGUS patients (median level 13 ug/mL), adiponectin levels were statistically significantly 
lower among those with smoldering (median level 10.9 ug/mL) and fully developed MM 
(median level 11.4 ug/mL) (p = 0.048). Adiponectin levels were also lower amongst those 
with the higher risk IgM isotype compared to those with IgG/IgA isotypes 6. Similarly, inverse 
associations with MM were observed for total adiponectin (OR = 0.49, Ptrend = .03) and high 
molecular weight adiponectin (OR = 0.44, Ptrend = .01). These associations remained after 
restricting to MM patients diagnosed ∼ 8 years or more after blood collection 11. 

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A prospective pooled analysis of 7 cohorts, comparing 624 MM cases with 1246 matched 
controls, showed that higher total adiponectin levels were associated with reduced MM risk 
overall (OR 0.64 [95% CI 0.47-0.85]). The study also observed strong associations among 
subjects who were overweight or obese (OR 0.41 [95% CI 0.17-0.98]) but not among those 
with normal weight (OR 1.20 [95% CI 0.73-2.00]). This study provides the strongest 
epidemiologic evidence that adiponectin protects against MM development particularly in 
overweight and obese individuals.7 Therefore, we hypothesize that weight loss will lead to 
increased adiponectin levels, a surrogate marker for reduced risk of progression to MM. 
Figure 3: 
 
 
 
Link between bone marrow adipocytes in overweight/obese patients and MM: Chronic 
immune responses against lipid antigens have been proposed as a driver of MM 
pathogenesis41. In mouse models, researchers showed that diet-induced obesity creates a 
permissive environment for the development of an MGUS-like condition, associated with 
myeloma cell accumulation in BM, an increase in serum paraprotein and mild bone loss42. 
Adipocyte stem cells were obtained from normal, overweight, obese or super obese patients. 
Adipocyte conditioned media from obese and super obese patients significantly increased 
MM cell adhesion, and conditioned media from overweight, obese and super obese patients 
enhanced tube formation and expression of matrix metalloproteinase-2 suggesting that 
adipocytes in the MM microenvironment contribute to MM growth and progression43. 

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Methods to evaluate body composition in MM: Most studies evaluating body composition in 
MM or precursor disorders have used BMI as a clinical measure of obesity and body fatness 
and shown significant associations as described above. Although, this is easy to calculate for 
all patients it has its limitations. It is a surrogate measure for body fatness because it is a 
measure of excess weight rather than excess body fat. Factors such as age, gender, 
ethnicity, muscle mass can influence the relationship between BMI and body fat. Limited 
studies in myeloma have shown that in cases where BMI did not correlate with treatment 
response or clinical parameters the CT scan was able to identify significant correlations given 
it is a more sensitive test for body fatness. These scans are also able to differentiate total 
body fat, subcutaneous body fat and visceral body fat.44 
The PET scan is a cornerstone in the initial work-up for newly diagnosed plasma cell disorder 
patients, since it has the highest sensitivity to detect osteolytic bone lesions. Furthermore, it 
offers the opportunity to image and quantify the extent of visceral and subcutaneous adipose 
tissue as a side product. MRI based body composition analyses have also shown between- 
scanner reproducibility and repeatability.45 PET MRI has the added advantage of being able 
to quantify bone marrow adiposity as well. 
Impact of metabolic disorder induced epigenetic changes in T cells leading to immune 
dysfunction: T cell exhaustion in early tumorigenesis has been recently found to be mediated 
by epigenetic reprograming of chromatin, inducing a non-plastic and non-responsive state.46 
Interestingly, metabolic pressure is 
also associated with epigenetic 
changes in T cells, although the 
mechanism is not clear.46-49 While 
epigenetic immune cell 
dysregulation is implicated in both 
MM development and T cell 
exhaustion, the molecular 
mechanisms driving these changes 
are largely unknown. The Yael 
David laboratory at Memorial Sloan 
Kettering Cancer Center (MSK) 
recently found that metabolic stress 
can induce major changes in 
chromatin structure and function 
through chemical glycation of 
histone proteins, which are major 
epigenetic regulators that spool the 
DNA.50 Importantly, they identified 
DJ-1 and PAD4, known oncoproteins 
in several cancers including 
MM,51,52,53 as potent enzymatic 
Figure 4: Histone glycation disrupts chromatin architecture and the 
epigenetic landscape. ATAC-seq analysis of cells treated with 
methylglyoxal (MGO: a reactive compound that is implicated in 
diabetes) show (a) decreased accessibility in general and (b) at 
transcription start sites. (c) Enzymatic histone modifications are 
disrupted by glycation. (d) RNA-seq analysis of MGO-treated cells 
indicate significant alterations in gene expression upon histone 
glycation. 

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Figure 5: Model for the mechanistic link between metabolic stress and impaired T cell function. In this model, metabolic 
or mutational stress cause cellular transformation and nucleation of a transformed cell. T cells utilize glucose in the blood 
stream to promote cellular proliferation and generate reactive metabolic byproducts that react with histones and eventually 
lead to changes in chromatin structure and function. An aberrant cellular epigenetic state contributes to changes in the 
transcriptome, leading to cellular transformation. 
regulators of histone glycation (Figure 4).50 In diabetes/hyperglycemia, metabolic stress is an 
important factor to which circulating cells, such as T cells, are exposed through high and 
unstable blood sugar levels (Figure 5). We hypothesize that histone glycation might play a 
role in driving epigenetic changes in these cells. Herein, we propose to investigate the 
consequences of metabolism-related chromatin damage for peripheral blood T cell function 
in MM. 
 
 
 
 
Link between the diet and microbiome in MM: Prior data from studies conducted at MSK has 
shown that increased relative abundances of Eubacterium hallii and Faecalibacterium 
prausnitzii in the gut associates with deep responses to MM therapy (Figure 6).54 Patients 
with MM who have received an allogeneic stem cell transplant have higher graft-versus- 
tumor (GVT) immune activity when levels of Eubacterium limosum are high in gut 
microbiota.55 Given that these three species of bacteria facilitate production of short-chain 
fatty acids (SCFA) such as butyrate and acetate, these results suggest that those products 
improve outcomes in MM. Gut paneth cells are one of the sources of adiponectin, which they 
produce in response to microbial stimuli. Abundance of Faecalibacterium Prausnitzii has a 
positive correlation with serum adiponectin levels and reduced abundance of this microbe 
has been observed in obese individuals when compared with non-obese individuals.56 Taken 
together these observations suggest a link between gut dysbiosis, metabolism and MM. 

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Figure 6: Fecal microbiota analysis according to minimal residual disease (MRD) status [MRD (-): absence of disease, 
MRD (+): presence of disease]. (a) Linear discriminant analysis (LDA) effect size analysis of microbiota differentially 
associated with MRD status with subclass of autologous stem cell transplantation (ASCT). (b) Relative abundance of genera 
Eubacterium and Faecalibacterium by MRD status. 
 
 
 
 
 
Butyrates, produced by saccharolytic anaerobes, inhibit histone deacetylases as well as the 
NF-κB pathway, which plays a critical role in the development of myeloma.57 Butyrates 
modulate immunity by exerting anti-inflammatory functions through inhibition of the 
transcription factor NF-κB, leading to reduced formation of proinflammatory cytokines. They 
also non-competitively inhibit histone deacetylases (HDAC),58 acting in the same way as 
panobinostat, an HDAC inhibitor with activity in MM. We hypothesize that the role of 
butyrates in these mechanisms decreases the likelihood of progression to MM. 
Diet plays a substantial role in shaping the microbiome, and dietary alterations can induce 
large microbial shifts within short periods of time (even 24 h).28,59-62 Fecal concentrations of 
short-chain fatty acids such as butyrate and acetate from carbohydrate metabolism by 
saccharolytic microbes are higher when individuals eat a plant-based rather than an animal- 
based diet; those who eat an animal-based diet have a higher proportion of microbiota 
producing short-chain fatty acids such as isovalerate and isobutyrate from amino acid 
fermentation.61 Thus, it is plausible that dietary factors alter gut microbial composition and 
impact disease outcomes, providing a strong rationale for systematically investigating the 
relationship between diet and microbiome in plasma cell disorders. 
Overall study objectives: As described above, a whole food, plant-based diet (WFPBD) may 
be beneficial, as there is evidence that it is associated with reduced BMI and increased 
adiponectin levels as well as alterations of the microbiome.28,59-61 No dietary trial has yet 
tested a WFPBD in patients with MGUS and SMM. Preliminary data provide a strong 
rationale to conduct a pilot study testing whether such a diet will lead to weight loss and 

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changes in biomarkers of disease, serving as surrogate markers for risk of progression to 
MM, in obese and overweight patients with MGUS and SMM. 
 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
4.1 
Design 
This is a single-arm, single-center pilot study with 20 patients who will be administered a 
whole-foods plant-based diet for 12 weeks with nutrition counselling for 24 weeks. 
4.2 
Intervention 
Treatment plan: For 12 weeks, patients will receive two premade meals per day, for lunch 
and dinner, prepared and shipped weekly by U.S.-based WFPBD company Plantable. The 
meals will have a low glycemic index and contain vegetables, whole grains, and plant-based 
fats that have undergone minimal processing. Instructions will be provided for food storage 
and reheating. Detailed recommendations for snacks and breakfasts meeting the standard of 
a WFPBD will also be given to supplement their daily calorie needs with access to an online 
portal from Plantable which contains education materials and access to a coach daily for 24 
weeks. Patients will also receive dietary education and counselling from a research dietitian 
every 2 weeks for the 12-week intervention period and then at 18 and 24 weeks. They will 
have access to the team for questions and support as needed. Upon joining the trial, patients 
will receive vitamin repletion of folate, iron, vitamin B12, and vitamin D to within the normal 
range if necessary. 
Plantable has seen the following results in 28 days with their program (Table 3). 
Table 3: 

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Figure 1: 
 
 
 
 
 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS 
The only therapeutic agents being tested in this trial is a plant-based diet, a non- 
pharmacologic agent. 
6.0 
CRITERIA FOR PARTICIPANT ELIGIBILITY 
6.1 
Participant Inclusion Criteria 
• 
BMI ≥25 
• 
Confirmed diagnosis of MGUS or SMM 

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• 
M spike (immunoglobulin) ≥0.2 g/dL or abnormal free light chain ratio with increased 
level of the appropriate involved light chain 
• 
Secretory disease 
• 
Age ≥18 years 
• 
Willingness to comply with all study-related procedures 
• 
ECOG performance status of 0-3 
• 
Interest to learn to cook plant based recipes 
 
 
6.2 
Participant Exclusion Criteria 
• 
Patients that already follow a whole foods plant based or vegan diet (ovo-lacto- 
vegetarian diets are not excluded) 
• 
Legume allergy 
• 
Severe allergies, such as anaphylactic shock to peanuts 
• 
Concurrent participation in weight loss/dietary/exercise programs 
• 
Mental impairment leading to inability to cooperate 
• 
Enrollment onto any other therapeutic investigational study 
• 
Concurrent pregnancy 
• 
Patients with a known diagnosis of diabetes mellitus will not be excluded but will need 
to be followed regularly with an endocrinologist/primary care physician during the trial 
period. 
• 
Positive HBV, HCV, HIV PCR testing 
• 
Non English speaking 
• 
≥ Grade 2 electrolyte abnormalities as defined by CTCAEv5.0 (need to be resolved 
before enrolling on study) 
• 
If in the opinion of the investigator there maybe any concerns regarding the ability of 
the patient to complete the study safely 
7.0 
RECRUITMENT PLAN 
7.1 
Research Participant Registration 
 
This study is a single center pilot study in MGUS and SMM patients. Efforts will be made to 
ensure that women and minority groups are adequately represented in this trial. All patients 
will be seen by myeloma physicians and associated co-investigators, enrolled and registered 
at the study site. Patients seen at the study site will be screened for eligibility. 
All co-investigators agree to follow the treatment in the protocol and to conduct the proposed 
investigation according to recognized principles of good clinical practice. Participation is 
voluntary. Each patient must be informed about the nature of his/her disease and willingly 
consent to participation in this study. Every patient will be informed of the procedures to be 
followed, the potential benefits, side effects, risks, and discomforts of the trial and of potential 
therapeutic alternatives. All participants will be required to sign statements of informed 
consent and research authorization that conform to the FDA, IRB and HIPAA guidelines. 
Informed consent will be documented by the use of a written consent form that has been 

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approved by the MSKCC IRB. In the Networks, physicians will directly refer patients for 
screening and protocol consideration. In addition, all new visits are screened by the study 
coordinators for protocol eligibility. 
 
7.2 
Randomization 
This is a non-randomized study. 
7.3 
Accrual 
We plan to accrue a total of 23 patients but have accounted for an anticipated 20% dropout 
rate and will replace up to 4 patients that may drop out from the trial within the initial 12 week 
intervention period. If additional patients drop out beyond the first 4 then they will not be 
replaced and included in the feasibility analysis. 
At MSK we have >10,000 patient visits for plasma cell disorders annually, including ~200 
new and ~1000 established patients with MGUS/SMM. About 2/3 of our patients will be 
overweight or obese, and thus eligible for this study.4 
We expect to accrue 2-3 patients per month for a total accrual period of 10 months. The 
study will be completed 52 weeks after the last patient enrolls, and therefore an estimated 
date of completion would be 22 months from study opening. 
8.0 
INFORMED CONSENT PROCEDURES 
Before protocol-specified procedures are carried out, consenting professionals will explain 
full details of the protocol and study procedures as well as the risks involved to participants 
prior to their inclusion in the study. Participants will also be informed that they are free to 
withdraw from the study at any time. All participants must sign an IRB/PB-approved consent 
form indicating their consent to participate. This consent form meets the requirements of the 
Code of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. 
The consent form will include the following: 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information. In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 

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Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
9.0 
PRE-TREATMENT/INTERVENTION 
9.1 Screening Period 
The screening period consists of initial patient review and informed consent. Patients 
consented who do not subsequently meet eligibility criteria will be registered as a screen fail. 
9.2 Baseline Study Assessments 
Study related assessments will be conducted no more than 28 days prior to the start of 
treatment. Baseline assessments include the following: 
1. Vital signs including (temp, PR, RR, BP and O2 saturation), height, weight, BMI 
calculation and waist circumference. 
2. Routine labs which include: 
- 
CBC with differential 
- 
Comprehensive Metabolic Panel 
- 
Magnesium, phosphorus 
- 
TSH, uric acid, LDH 
- 
BNP, NT-Pro-BNP, troponin I 
- 
Serum protein electrophoresis (SPEP) and immunofixation to assess for presence 
- 
and quantity of monoclonal protein (M-protein), Serum free light-chains, quantitative 
immunoglobulins (IgA/IgG/IgM), IgD, IgE, beta 2-Microglobulin 
- 
Fasting metabolic labs: CRP, ESR, fasting lipid profile, fasting glucose, HgbA1c. 
- 
A random urine sample for protein electrophoresis (UPEP) and immunofixation to 
assess for monoclonal protein in the urine (Bence-Jones proteinuria). 
3. Vitamin Levels: Vitamin D, Vitamin B12, folate, iron/TIBC, ferritin 
4. Fasting research blood draw and hematology oncology tissue bank (HOTB) storage 
(Metabolic Labs for Pollack Lab: IL-6, insulin, IGF-1, adiponectin, leptin) 
5. Viral studies: Hepatitis B surface antigen, Hep B surface antibody, Hepatitis B core 
antibody, HIV 1 & 2 antibody, Hepatitis C (HCV) antibody (within 24 weeks prior to 
baseline). 
6. Bone marrow core biopsy and/or aspirate with flow cytometry and HOTB banking. (as 
long as bone marrow is collected and sample banked with HOTB within 24 weeks prior to 
baseline study assessment then repeat biopsy will not be required). 
7. Serum or urine pregnancy test in women of child-bearing potential. 
8. A baseline 12-lead EKG within 3 months prior to baseline study assessment. 
9. A baseline whole-body (WB) MRI or PET/MRI (preferable) or low dose whole-body CT or 
PET/CT will be performed on all patients at screening (within 12 weeks prior to screening 
visit). Preference will be given to MRI or PET MRI however, if claustrophobic or any 

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other contraindication to MRI then they will get WB CT or PET CT per investigator 
discretion. 
10. Patient-reported outcomes questionnaires 
11. Block Survey 
12. Stool collection 
10.0 TREATMENT/INTERVENTION PLAN 
Patients who undergo screening and are deemed eligible by above criteria for the study, 
undergo all necessary pre-treatment testing and biospecimen collection. 
Evaluation Prior to Initiation of Intervention 
The study intervention is designed to reduce fat mass and maintain or increase lean mass 
through a fiber rich diet. We will determine energy needs using the Mifflin-St. Jeor equation 
accounting for patient’s physical activity level at baseline. Patients will be given a list of foods 
to eat and foods to avoid beyond the meals provided. Patients will eat to satiation with no 
calorie restriction. 
Study Interventions 
As defined, the study intervention/treatment approach will consist of a whole foods plant- 
based diet. Pre-prepared meals, including 6 dinners and 6 lunches per week, will be shipped 
to the participant’s home for the 12 week intervention period. The nutrition counselling will 
guide them to eat a healthy whole foods plant based diet for 24 weeks. 
Whole Foods Plant-based Diet 
Meals will be provided by Plantable (FDA Registration #17996628280). Pre-packaged, 
frozen plant-based meals (6 lunches and 6 dinners) will be delivered weekly to participants’ 
homes. Each meal is created to have the appropriate mix of macronutrients intake (e.g., 
carbohydrate, protein, and fat), consistent with USDA dietary guidelines, and to provide 
satiety. Meals are made with whole ingredients spanning whole grains, vegetables, legumes, 
nuts and seeds. Added sugar or animal based products are not used in any meal. Meals are 
produced, packaged, stored and shipped from the Plantable kitchen and storage facility 
located at 630 Flushing Avenue, Brooklyn, NY 11206. Plantable is regulated by the New 
York State Department of Agriculture and Markets and adheres to the New York State 
Department of Health Food Safety Regulations. Inspectors regularly visit the premises and 
the company has no history of violations. All management/chef level kitchen employees are 
certified in food safety by the state of New York. The principal food suppliers are Ace Natural 
and Baldor Food, HACCP accredited wholesale produce and specialty goods suppliers. 
Produce is shipped via refrigerated trucks and stored in a walk-in refrigerator unit at or below 
38 degrees Fahrenheit. Meals are cooked and cooled in an ice bath within 2 hours. Meals 
are then stored overnight at or below 38 degrees Fahrenheit in a walk-in refrigerator unit. 
Meals are packed, in batches using 3-mil Poly Nylon food storage bags (FDA/USDA 

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compliant and BPA free). These bags are sourced from Uline and Imperial Paper. Completed 
and packaged meals are then frozen and stored at or below 0 degrees Fahrenheit in a walk- 
in freezer unit until individually packed for study participants. For shipping (materials sourced 
from Allboxes), meals are packed with frozen gel ice packs in corrugated boxes with 
recyclable, eco-friendly additional insulation. Packages are shipped via UPS, one and two 
day ground or air, depending on final destination. 
Instructions will be given on food storage and reheating with each shipment. All participants 
will receive written documents which include the list of ingredients, nutritional label along with 
full heating and meal storage instructions. During the 12 week intervention, 6 lunches and 6 
dinners will be delivered to participants weekly. Participants will be responsible for preparing 
their own plant-based breakfasts for all days, and all plant-based meals one day per week. 
Educational materials and recipes will be sent daily (via email) for the first 28-days and made 
available via an online portal to participants to encourage the replacement of nutrient-poor, 
high energy foods with nutrient-rich, low energy plant-based foods (i.e., vegetables, fruits, 
whole grains). Coaches will also be available to participants from 7AM – 11PM, 7 days per 
week throughout the 24 week study period via telephone or text messaging to answer 
questions or concerns regarding food preparation or food choices, particularly for self- 
prepared breakfasts, snacks, and all meals one day per week. 
Participants will also have access to the Plantable app, which does not collect or retain any 
participant information. This app includes: 
1. Recipes - 100+ curated plantable approved recipes, designed to be plant-based, nutrient- 
dense, filled with plant-based protein for satiety. No added sugar, no refined grains. 
Balanced and easy. 
2. Menu planning - and integration into shopping list 
3. Ability to integrate with plantable home-delivered fully prepared meals 
4. 28-day educational content to accompany the journey 
5. How-to Series - a educational library spanning nutrition and well-being education 
6. One-on-one access to a personal coach 
7. Tracking - meals, water, movement etc. 
(Appendix F, G, H) 
 
Food intake will be monitored using food logs and 72 hour dietary recall. Study staff will use 
the online web based ASA-24 application - 
https://epi.grants.cancer.gov/asa24/respondent/2020.html. Participants will use daily food 
logs to record the percentage of food eaten for each delivered meal and foods consumed for 
breakfast and snacks. The food log for each day of the study will be included with the weekly 
meal delivery. Dietary intake will be reviewed every 2 weeks by an MSK registered dietitian 
to assess adherence and tolerance of diet plan. Participants will be weighed at each visit. 
The nutrition consultation will consist of identification and counseling for major nutritional 
deficiencies and a nutritional program consistent with American Cancer Society guidelines, 

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which may include nutritional supplements (e.g., calcium, vitamin D, vitamin B12) as 
necessary. Patients will be asked to take a weekly vitamin B12 supplement of 1000 mcg 
while on this diet. Vitamin D levels must be maintained over 30 ng/mL with supplementation 
as needed. Dietary intake will be assessed using food logs and 72 hour recall. The staff 
registered dietitian will contact patients to check progress and answer questions. Dietary 
assessments by the MSK research dietitian will be done via phone visits alternating with in 
person visits every 2 weeks. (Appendix J) 
Participants will be asked to complete a food log for the week prior to research dietitian visit 
at week 18 and week 24 as well. 
11.0 EVALUATION DURING TREATMENT/INTERVENTION 
 
 
Table 4: Schedule of activities 
 
Assessment 
Screening 
C1D1 
Day 1 
C1D8 
Day 8 
C2D1 
End 
of wk 
4 
C3D1 
End 
of wk 
8 
C4D1 
Post- 
Interve 
ntion 
(End of 
12 wks) 
C7D1 
Sustained 
Post- 
Intervention 
(end of 24 
wks) 
End of 
study 
(end of 
52 
wks) q 
If 
progresses 
to MM while 
on studyp 
Timepoint 
Baseline 
(Up to 6 
weeks prior 
to D1) 
Day 1 
(± 7d) 
Day 8 
(± 7d) 
Day 
28 
(± 7d) 
Day 
56 
(± 7d) 
Day 
84 
(± 7d) 
Day 
168 
(± 7d) 
Day 
365 (± 
7d) 
(± 7d) 
History/physical* 
X 
X 
X 
X 
X 
X 
X q 
Xp 
Vital signs, ht, wt, 
BMI, waist 
circumference 
(Appendix K) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Routine labsa 
X 
X 
X 
X 
X 
X 
X 
X 
Viral studiesb 
X 
Pregnancy testc 
X 
Vitamin levelsd 
X 
X 
X 
Metabolic labse 
X 
X 
X 
X 
Urinary myeloma 
testsf 
X 
if pt goes into complete remission; additional time points if clinically indicated 
Research bloodg 
X 
X 
X 
X 
X 
X 
X 

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Imagingh 
X 
X 
X 
BM biopsyi,j 
X 
X 
X 
Stoolk 
X 
X 
X 
X 
X 
X 
Research dietitian 
visitl,m 
Xn 
Xn 
X 
X 
X 
X 
X 
Block FFQ 
X 
X 
X 
X 
X 
CTCAEv5.0o 
X 
X 
X 
X 
X 
QOL survey 
X 
X 
X 
X 
X 
X 
12-Lead-ECG 
Xr 
Post-Intervention 
Feedback Survey 
Xs 
X= required protocol assessment 
QOL: Quality of Life 
* - visits may be in person or via telemedicine depending on patient and dietitian location (main campus 
vs satellite) as long as labs, vitals and research samples are collected at MSKCC 
 
 
Additional laboratory studies and clinic visits may be performed as clinically indicated. 
a. Routine tests to be done at baseline will include: CBC with differential, comprehensive 
metabolic panel (including hepatic function, calcium, and albumin), phosphorus, 
magnesium,TSH, uric acid, lactate dehydrogenase, NT-Pro BNP, BNP, troponin I, serum 
electrophoresis (SPEP), serum immunofixation, serum free light chains, quanitative 
immunoglobulins (IgA/IgG/IgM), IgD, IgE, beta 2-microglobulins, and fasting metabolic labs: 
ESR, CRP, fasting lipid profile, fasting glucose, HgbA1c. At all other follow up visits patients 
will have the following labs done: CBC with diferential, comprehensive metabolic panel, 
phosphorus, magnesium, SPEP, serum immunofixation, serum free light chains, quantitative 
immunoglobulins, beta 2 microglobulin and fasting metabolic labs: ESR, CRP, fasting lipid 
profile, fasting glucose, HgbA1c. At Day 8 follow up visit labs will include: COMP. 
b. Viral studies include HIV 1 & 2, Hep B surface antigen, Hep B surface antibody, Hep B core 
antibody and Hep C antibody. If HIV, Hep B or C antibody positive, HIV, Hep B or C quantitative 
PCR will be performed. (These tests should be performed within the last 24 weeks.) 
c. Pregnancy tests (urine or serum) for females of childbearing potential. A female of childbearing 
potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or 
bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 
consecutive months (i.e., has had menses at any time in the preceding 24 consecutive 
months). 
d. Vitamin levels will include iron/TIBC, ferritin, vitamin B12, folate, vitamin D at marked 

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timepoints. If levels are low, then they will be repeated after repletion to achieve a normal goal. 
(vitamin D > 30 ng/mL and Vitamin B12 > 300 ng/L, rest will be based on parameters of normal 
range). 
e. The following labs will be sent to Pollak lab in batches IL-6, IGF-1, adiponectin, leptin, fasting 
insulin from stored HOTB samples. 
f. 
Urine random for protein electrophoresis (UPEP) and immunofixation to assess for monoclonal 
protein in the urine (Bence-Jones proteinuria) at baseline in all patients and if the patient goes 
into complete remission regardless of baseline urine M-spike values. If urine protein 
electrophoresis at baseline is positive for myeloma protein, then random urine samples will be 
checked if serum M spike is undetectable or normalization of free light chains. If baseline is 
negative, then urine for myeloma protein will not be checked again.63 Additional time points if 
clinically indicated. 
g. Research blood draw will include 4 CPTs for PBMCs, plasma and granulocytes and 1 SST for 
serum at baseline, week 12 and week 24. Research blood draw will include 2 CPTs for PBMCs, 
plasma and granulocytes and 1 SST for serum at week 4, week 8 and week 52. 
h. PET MR or WB MRI is preferred but PET CT or low dose WB CT is also acceptable and will 
be performed on patients at baseline within 12 weeks prior to day 1. Similar Imaging will be 
repeated before 52 weeks visit as a clinical standard of care study. The same modality CT/PET 
CT or MR/PET MR must be done at baseline and end of study. 
i. 
Baseline bone marrow aspirate and biopsy can be performed within 24 weeks prior to day 1 
as long as standard of care HOTB sample has been banked from that biopsy and as long as 
M spike/involved FLC is within +/-25% change from that time point. Bone marrow aspirate and 
biopsy will be sent to Dept of Pathology for flow cytometry, FISH/cytogenetics, and molecular 
studies (IgH rearrangement), as well as to HOTB for sorting and storage per HOTB SOPs. 
j. 
BM biopsy will be repeated as standard of care before 52 weeks if there is a >25% reduction 
in M spike/free light chain and HOTB samples will be collected. If there is no change in 
paraprotein or increase BM biopsy does not need to be performed. However, if at disease 
progression or for other clinical reasons, bone marrow biopsy is performed HOTB samples 
will be collected. 
k. Patients will receive materials and instructions to collect a stool sample at home. This sample 
will be sent to the molecular microbiology core facility for processing and analysis. 
l. 
Research dietitian visits - Participants will use 72 hour dietary recalls to record the 
percentage of food eaten for each delivered meal and foods consumed for breakfast and 
snacks. The food log for each day of the study will be included with the weekly meal delivery 
for 12 weeks and then will also be completed for week 18 and 24 prior to dietitian visit. Study 
staff will use the online web based ASA-24 application - 
https://epi.grants.cancer.gov/asa24/respondent/2020.html. 
m. Dietary assessments at the following time points (2, 6, 10, 18 weeks +/-3 days) by the MSK 
research dietitian will be done via phone visits. Other visits may be in person or via 
telemedicine depending on patient and dietitian location (main campus vs satellite). 
n. Research dietitians will briefly review the Appendix C, E, I, J information with the patient at 
their baseline visit and then go over the patients completed WFPBD information checklist 
(Appendix E) at their Day 1 visit. 
o. Monitoring for adverse events and toxicity will be done at every visit using CTCAEv5.0 criteria. 
p. Patients may be followed at more frequent time intervals if clinically indicated. Patients who 

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have progressive disease will be followed with restaging scans and laboratory tests as clinically 
indicated. 
q. Patients taken off protocol therapy for unacceptable adverse events will be followed until 
resolution or stabilization of the adverse event, and at least until 30 days after the last day of 
intervention. Further follow-up for survival will be assessed either by phone consultation or 
clinic appointment at the discretion of the PI. 
r. A baseline 12-lead EKG within 3 months prior to baseline study assessment 
s. All patients who have completed 1 year on study will be sent an optional post intervention 
feedback survey via Redcap for completion. 
 
 
BIOSPECIMEN COLLECTION 
1) Blood 
a. Research blood samples for biomarker studies will be collected from all patients at the timepoints 
listed above. 
The samples will be batched for later analysis. 
b. Specimens will also be collected and stored at the time of documented CR and disease progression. 
c. The standard number of peripheral blood tubes drawn for biomarker analysis, and storage for future 
assays at each of the above time points may include but are not limited to the following CPT tubes to 
store plasma, granulocytes and PBMCs and SST tube to store serum (At baseline, baseline, week 12 
and week 24 - 4 CPT and 1 SST; At 4, 8 and 52 weeks – 2 CPT and 1 SST). 
d. At any given time point when blood collection is performed per the study schedule, up to 100cc of 
peripheral blood will be collected. The amount of blood collected will be dictated by the number of 
experiments to be performed, and by the patient’s peripheral blood count. 
e. Sample Requirements and Handling: The date and exact time of each blood draw should be 
recorded on the sample tube. Serum samples should be kept at room temperature for 30-60min prior 
to being refrigerated. Samples will be submitted to HOTB for storage. 
f. Biomarker studies associated with peripheral blood specimen will be performed and related to 
clinical outcome if the results of the study indicate a clinical or translational rationale for analyzing the 
samples and provided sufficient sample obtained. Such studies may include but are not limited to the 
following: 
i. Epigenetic analysis of T cells 
ii. Flow cytometry including leukocyte subset analysis. 
iii. Gene expression analysis 
iv. Secreted inflammatory biomarkers such as Olink panels 
2) Bone Marrow 
a. Bone marrow specimens (aspirate) will be collected within 6 months from baseline and between 

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weeks 24 and 52 if there is a >25% reduction in M spike/free light chain and at the time of suspected 
CR or disease progression or investigator’s discretion. Bone marrow samples will be used to 
determine the molecular characteristics of tumor and non-tumor cells. 
b. At any given time point when a bone marrow aspirate is performed per the study schedule or for 
clinically indicated reasons 3-6mL bone marrow aspirate into two EDTA syringes/vials will be collected 
for research purposes. 
c. Sample Requirements and Handling: The date and exact time of each bone marrow collection 
should be recorded on the sample tube. Bone marrow aspirate samples will be submitted to HOTB for 
storage per protocol. Bone marrow core and aspirate will also be sent to the clinical lab per standard 
of care requirements. 
 
Priority 
Media 
Purpose 
Delivery Location 
1 – required 
10% NBF 
Standard of Care 
Surg path 
 
d. Biomarker studies associated with bone marrow specimen will be performed and related to clinical 
outcome if the results of the study indicate a clinical or translational rationale for analyzing the samples 
and provided sufficient sample obtained. Such studies may include but are not limited to the following: 
i. Pathology/Immunohistochemistry including but not limited to stains to measure adipocyte size. 
ii. Flow cytometry. 
iii. Gene expression analysis such as single cell RNA sequencing and CITE sequencing 
iv. Epigenetic analysis. 
v. Secreted inflammatory biomarkers such as Olink panels 
3) Stool: Gut microbiome: Stool will be collected at baseline,4 weeks, 12 weeks,24 weeks and 52 
weeks. Stool will be analyzed via 16S sequencing and/or shotgun sequencing in the Molecular 
Microbiology Core Facility and GCMS assays such as short chain fatty acids in the Castori 
center. 
BIOMARKER STUDIES: METHODS 
 
Future Assays: After planned analysis for this study is complete, anything left over will be stored in 
HOTB/David lab for future use under 06-107 and corresponding biospecimen protocols. Left over 
samples are those that remain after the correlative work for the study is completed. Consent will be 
obtained for patients who are not already enrolled onto 06-107. 
Future Use of Samples 
Banked tissue, stool, and blood samples, as appropriate, will be used for future correlative 
studies. Any projects outside of the scope of this protocol will need to be approved by the 
IRB/PB. In order for the researchers to have access to the leftover samples, participants will 
consent to protocol 06-107, and a biospecimen correlative protocol detailing the proposed 
project will need to be approved by the IRB/PB prior to initiation of any project. 

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12.0 CRITERIA FOR REMOVAL FROM STUDY 
Table 5. Primary Reasons for Permanent Intervention Discontinuation 
Reason 
Description 
Self-withdrawal 
(withdrawal 
of consent) 
Patients may permanently discontinue study intervention and 
withdraw from the study anytime for any reason. Following 
study intervention discontinuation, 
participants can have 
protocol-required safety follow-up and long-term follow-up 
assessments unless the participant specifically declines further 
follow-up. 
Adverse event or intercurrent 
illness 
Any intolerable adverse event (associated or not associated with 
the study intervention) that cannot be ameliorated by the use of 
adequate medical intervention or that, in the opinion of the 
investigator, would lead to undue risk if study intervention were 
continued. 
Gross noncompliance with 
protocol (violation) 
The investigator may consider permanent discontinuation in the 
event of lack of cooperation or complete noncompliance during 
the intervention period. 
Disease progression 
Study intervention will be discontinued upon evidence of clinical 
or radiographic disease progression to multiple myeloma 
determined by the patient’s oncologist and principal investigator. 
Lost to follow up 
Reasonable effort should be made to contact any participant lost 
to follow-up during the course of the study in order to complete 
study-related assessments and record outstanding data. 
Death 
If a patient dies while on study their data will be included up until 
their death and they will be taken off study. Cause of death will 
be evaluated for any association with study intervention. 
 
Additional patients will be accrued to maintain the target sample size in the event that a study 
participant does not complete the intervention period. Additional patients may be accrued to replace 
patients who discontinue the study intervention for any of the reasons listed in Table 4, however 
patients who discontinue the study intervention but have baseline lab assessments recorded will be 
included in the sensitivity/compliance analysis. 
 
13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY 
 
13.1 Criteria for Study Endpoint Evaluability 
Primary Endpoint: 

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1.  Weight loss: The primary objective of this study is to determine the effect of the diet to achieve a 
mean BMI reduction from baseline at 12 weeks. Patients will be weighed at the baseline/screening 
visit and after 4, 8, 12 and 24 weeks and their BMI will be calculated. All patients who have received 
a WFPBD intervention for 12 weeks and have both baseline and 12-week laboratory results 
recorded are evaluable for primary endpoint. Patients who withdraw or are withdrawn from the study 
prior to completing 12 week laboratory results will not be considered evaluable for primary endpoint. 
We will replace up to 4 patients that are not evaluable for primary endpoint. 
2.  Adherence: To achieve patient adherence to the intervention defined as ≥70% of participants 
consuming a WFPBD for ≥70% of meals of the 12-week intervention period (determined via a 
dietary recall and nutritional survey). A benchmark of 70% was chosen as it is the current 
benchmark for adherence in lifestyle trials64. Also understand long term adherence by evaluation of 
% of participants compliant at 24 weeks and 52 weeks based on 72-hour dietary recall and food 
frequency questionnaires. 
Patients will receive education from the dietitian about a WFPBD, including guidance on food 
choice and recipes. The research dietitian will contact patients every 2 weeks alternating 
phone and in-person visits to answer questions, providing personal coaching to ensure 
accountability and support. Adherence to phone visits will be retrospectively tracked from the 
patient’s EMR. Patients will complete a dietary food recall survey form for the 3 days prior at 
each monthly study visit, and the form will be used to assess compliance with the 
intervention. At each visit, the study assistant will also confirm the dietary recall with the 
patient. Patients will complete the Block Questionnaire (2014 full-length Food Frequency 
Questionnaire and Physical Activity Screener65,66) at baseline, 12 weeks, 24 weeks and 52 
weeks to assess adherence during and after the intervention and compare their pre- and 
post-intervention diet and activity. Participants will be asked to complete this survey via MSK 
Engage and a notification will be sent via email notification (Appendix M). Patients will be 
asked not to change their activity levels from baseline. Deidentified questionnaires will be 
sent to Nutrition Quest, which will use them to estimate nutrient intake and physical activity, 
returning the data in an electronic file suitable for statistical analysis 
(https://nutritionquest.com/assessment/).65,66 Patients who consume a WFPBD for ≥70% of 
the meals during the 12 weeks on study (determined by the dietary food recall survey) will be 
deemed to adhere to the intervention. If ≥70% of patients meet this requirement then the 
study will meet its objective for overall adherence for the trial. This benchmark was chosen 
because it is used generally to measure adherence in lifestyle trials. 
All patients who have received at least one WFPBD intervention are considered to be 
evaluable for assessment of adherence. Patients who withdraw or are withdrawn from the 
study prior to completing assessment at 12 weeks will be considered as failures for this 
endpoint. 
Secondary endpoints 

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1.  Safety: To determine safety at 12 weeks as determined by evaluating toxicity grading at 
each visit of the intervention, according to CTCAE v5.0 criteria. 
Toxicity grading will be performed in accordance with NCI Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0 at each study visit. Unanticipated but possible side effects of 
the plant-based meals include nausea, vomiting, diarrhea, and dyspepsia. It is possible but 
unexpected that patients would not tolerate this diet change and develop side effects such as 
bloating and diarrhea. High-fiber diets can lead to initial bloating that is expected to subside. 
Every effort will be made to provide education to prevent bloating while maintaining 
compliance by providing handouts on how to manage bloating as well as education during 
dietitian visits. 
All patients who have received at least one WFPBD intervention and had safety assessment 
are evaluable for the assessment of safety. 
2.  Quality of Life: To assess patient-reported outcomes at 4, 12, 24 and 52 weeks compared 
to baseline via patient completion of the EORTC QLQ-C30 surveys. 
Patients will complete the European Organization for the Research and Treatment of Cancer 
Quality of Life Questionnaire (EORTC QLQ-C30; 30 questions related to symptoms over the 
past week)67 at baseline, 4, 12 24 and 52 weeks to assess changes in their quality of life. 
Participants will be asked to complete this survey via MSK Engage and a notification will be 
sent via email notification (Appendix L). 
All patients who have received at least one WFPBD intervention and completed post 
baseline EORTC QLQ-C30 survey are considered to be evaluable for the quality of life 
assessment. 
3. Weight loss: To determine the effect of the diet to achieve a sustained mean BMI 
reduction from baseline at 24 and 52 weeks. All patients who have received at least one 
WFPBD intervention with weight measured at baseline and at 24, or 52 weeks are 
considered to be evaluable for the assement. 
3. Metabolic Markers: To assess changes in serum biomarkers such as adiponectin and 
leptin (markers of metabolic risk); HgbA1c, IGF-1, and insulin (markers of glucose 
metabolism); erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IL-6 
(markers of inflammation); and low-density lipoproteins (LDL; lipid profile) at 12, 24 and 52 
weeks compared to baseline. 
All patients who have received at least one WFPBD intervention with biomarker measured at 
baseline and at 12, 24, or 52 weeks are considered to be evaluable for the metabolic marker 
assessment at 12, 24, or 52 weeks compared to baseline. 
Adiponectin, leptin, ESR, CRP, IL-6, insulin, IGF-1, HgbA1c, and lipid profile will be checked 
at baseline, 12, 24 and 52 weeks. Fasting blood will be collected at the specified time points 
(see Schedule). Serum lipids including total cholesterol, high- and low-density lipoprotein 

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(HDL, LDL), triglycerides, ESR, high-sensitivity CRP (hsCRP), and HgbA1c will be measured 
at MSK and will be analyzed by the clinical laboratory. Serum and plasma will be separated 
and stored at –80°C in the Hematology Oncology Tissue Bank (HOTB). To prevent 
unnecessary freeze-thaw cycles, plasma and serum will be stored in ten 0.25 mL aliquots. . 
Blood samples will be analyzed in batches and blinded internal quality controls will be 
included to ensure consistency of the assays. Samples for analysis of plasma levels of 
leptin, adiponectin, IGF-1, IL-6, and insulin will be sent to the Michael Pollak laboratory at 
McGill University in Canada in batches (https://www.mcgill.ca/assaylab/assays). 
• 
Specimens should be labeled with the following – Nutrivention, MSKCC, Subject ID, 
Specimen ID, Subject Initials, Date of Collection/Time of Collection. (Participant identifiers do 
not need to be shared.) 
• 
Documents to be sent with the specimens – Requisition showing the sample ID, assay order, 
the box number, the grid position and analytes (e.g. adiponectin, insulin, IL-6, etc). They also 
require the electronic version of the requisition via email. 
• 
Specimens are to be shipped to: 
Rhoda Lim 
Dr. Pollak’s Lab, room E-423 
Lady Davis Institute 
Jewish General Hospital 
3755, Cote-Ste-Catherine Road 
Montreal, Quebec 
Canada H3T 1E2 
Tel.: (514) 340-8222 ext. 24139 
• 
Specimens are to be shipped with plenty of dry ice in an insulated shipping container. It is to 
be shipped on either on a Monday or a Tuesday so that the lab will receive the shipment on a 
weekday. Shipments will be sent preferably via World Courier or FedEx. World Courier 
replenishes the dry ice, while FedEx does not. 
• 
The specimens are to be tracked in CRDB. 
• 
The results will be sent from Pollak lab to MSK as an EXCEL spreadsheet. 
4. Myeloma Markers: To assess changes in serum paraproteins (quantitative 
immunoglobulins, free light chains and serum protein electrophoresis) at 4, 8, 12, 24 and 52 
weeks compared to baseline. 
The standard myeloma paraproteins—quantitative immunoglobulins, free light chains, serum, 
and urine protein electrophoresis (M-spike)—will be checked at baseline and at 4, 8, 12, 24 
and 52 weeks. Bone marrow biopsies will be done at baseline and then as clinically indicated 
subsequently.63 
All patients who have received at least one WFPBD intervention with biomarker measured at 
baseline and at 12, 24, or 52 weeks are considered to be evaluable for the myeloma marker 
assessment at 12, 24, or 52 weeks compared to baseline. 

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Exploratory Endpoints 
1. Epigenetic: To assess metabolism-related chromatin damage (epigenetic changes) in 
peripheral blood T cells (CD4 and CD8) at 12 weeks compared to baseline. 
If there is a significant change in weight, myeloma or metabolic biomarkers between baseline 
and 12 weeks then we will proceed with assessing epigenetic changes. To assess the 
epigenetic landscape, we will analyze at high-resolution the chromatin architecture, histone 
marks, and overall transcriptome of peripheral blood T cells (CD4 and CD8). This work will 
be performed in collaboration with the Yael David laboratory and the Center for Epigenetics 
Research at MSK. Specifically, we will sort peripheral blood T cells, extracted at baseline and 
12 weeks , into CD4 and CD8 subsets. We will then analyze their chromatin structure 
(ATAC-seq), transcriptomics (RNA-seq), and the epigenetic landscape (histone mass 
spectrometry), focusing on changes in histone modifications that are characteristic of MM 
and correlations to sites of glycation (Figure 4).50 
All patients who have received the WFPBD intervention with biomarkers measured at 
baseline and 12 weeks are evaluable for the epigenetics assessment. 
 
 
2. Microbiome: To assess shifts in the fecal microbiome measured by increase in diversity and 
relative abundance of butyrate-producing 
bacteria. 
Stool samples will be collected at 
baseline, 4 weeks, 12 and 24 weeks and 
frozen at -80℃ until ready for 
sequencing. DNA will be extracted and 
subjected to amplification of the V4/V5 
variable regions of the 16S ribosomal 
RNA genes using barcoded primers 
targeted to conserved sequences.68,69 
Purified polymerase chain reaction 
products will be sequenced on the 
Illumina MiSeq platform and 16S paired- 
end reads will be merged and 
demultiplexed. The UPARSE pipeline will 
be used to perform quality and error 
filtering using maximum expected error 
(Emax = 1), and reads with >97% identity will be grouped into operational taxonomic units 
(Figure 7).70 This aim will be performed in collaboration with Dr. Lesokhin, the Castori 
Center, and the van den Brink laboratory.54 We will also measure stool short chain fatty acid 
Figure 7: Proposed workflow uses bioinformatic techniques to 
evaluate relationship of microbiota with clinical outcomes. 

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levels at 4, 12,24 and 52 weeks compared to baseline with gas chromatography-mass 
spectrometry and consider shotgun sequencing of certain timepoints.71 
All patients who have received at least one WFPBD intervention with biomarker measured at 
baseline and 12 weeks are evaluable for the microbiome assessment. 
3. Immune: To assess changes in immune function as determined by peripheral blood 
leukocyte subsets via flow cytometry and bone marrow single cell RNA, ATAC, and CITE 
sequencing. 
All patients have peripheral blood at multiple timepoints and bone marrow biopsies at two 
time points – baseline and 12 months will be evaluable. This will be done in collaboration 
with IDMS core laboratory and van den Brink laboratory. 
4. Adiposity imaging: To assess changes in body composition (visceral, subcutaneous and 
bone marrow fat) as determined on PET CT or MR imaging and correlate these with weight 
changes as well as markers of disease. 
All patients that have imaging at two time points - baseline and between 6-12 months 
will be evaluable. These two time points will be compared for visceral, subcutaneous and 
bone marrow fat. These fat quantification measurements will be obtained from the PET scan 
with the help of radiologist Dr Marius Mayerhoefer using automated software previously 
described.72 These results will then be correlated with clinical changes in BMI, metabolic 
markers and paraproteins at two time points - baseline and 24 weeks. 
14.0 BIOSTATISTICS 
14.1 Populations for Analyses 
 
Sample size justification: We aim to enroll 20 obese or overweight patients (BMI ≥25) with MGUS or 
SMM. Previous data28 suggest that ~20% may drop out however up to 4 patients that do not complete 
12 weeks assessment will be replaced. All patients that have assessments at 12 weeks are evaluable 
for the primary endpoint of weight loss and all patients that received WFPBD including those that are 
not evaluable for the primary endpoint will be included in adherence analysis. The sample size for this 
study is driven by the primary aim to test whether a WFPBD leads to weight loss in obese/overweight 
MGUS/SMM patients and patients that drop out prior to 12 weeks will be replaced. Weight loss is 
defined as the average decrease in BMI at 12 weeks. On the basis of previous28 and internal studies, 
we assume that the mean and standard deviation of BMI at baseline will be 30 and 4.5, and that the 
standard deviation at 12 weeks will be similar. Using these assumptions, Table 1 shows the power for 
a paired t-test with a one-sided type I error of 0.1 to detect a decrease in BMI at 12 weeks from the 
baseline in a pilot study with 20 patients. We do not know the exact within-person correlation between 
two BMI measurements that are 12 weeks apart, but we expect it to be ≥90%. With these assumptions, 
we expect the study to be adequately powered to detect a clinically relevant difference of ≥5% from 
baseline to the end of the intervention. 

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Table 6: Expected power to detect BMI differences of varying magnitude with 20 patients 
Within-person correlation (N=20) 
Mean difference (%)* 0.7 
0.8 
0.9 
1.2 (4%) 
58% 
71% 
91% 
1.5 (5%) 
73% 
85% 
98% 
1.8 (6%) 
83% 
93% 
99% 
*Average BMI at baseline is assumed to be 30. 
Statistical Analysis: 
Primary Objective: 
The primary objective of the pilot study is to determine the feasibility of a WFPBD in 
obese/overweight patients with MGUS or SMM, as measured by weight loss and adherence. Weight 
loss due to WFPBD intervention is defined as the average decrease in BMI at 12 weeks. Adherence 
will be estimated by sample proportion, with confidence intervals calculated based on exact binomial 
distribution. 
Patients who have completed evaluation at 12 weeks will be evaluable for weight loss outcome . The 
average weight loss from baseline at 12 weeks s will be reported as sample mean along with 95% 
confidence interval. Adherence will be estimated by sample proportion, with confidence intervals 
calculated based on exact binomial distribution. All patients who have received at least one WFPBD 
intervention are considered to be evaluable for assessment of adherence. Patients who withdraw or 
are withdrawn from the study prior to completing assessment at 12 weeks will be considered as 
failures for this endpoint. 
We will call WFPBD promising if 1) we detect weight loss at 12 weeks and 2) estimated adherence to 
the intervention is ≥70%. 
Given our study's small sample size, we will not report results stratifying overweight and obese. In 
future randomized intervention study planning, we will evaluate the relationship between baseline BMI, 
weight loss, and adherence, using logistic and linear regressions. If a strong relationship between 
baseline BMI and primary endpoints is observed, stratification by BMI will be implemented into the 
study design. 
Secondary Objectives: 
1. The feasibility of WFPBD in obese/overweight patients with MGUS or SMM will measured by 
safety, and quality of life at 12, 24 and 52 weeks. Toxicities and adverse events will be reported 
descriptively. Change in quality of life at 12, 24, and 52 weeks from a baseline will be reported 
as sample mean along with 95% confidence interval. 
2. The average weight loss from baseline at 24 and 52 weeks s will be reported as sample mean 
along with 95% confidence interval. 
3. Alterations in metabolic, and myeloma markers secondary to a WFPBD intervention will be 

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assessed by changes in serum biomarkers such as adiponectin and leptin (markers of 
metabolic risk); HgbA1c, IGF-1, and insulin (markers of glucose metabolism); erythrocyte 
sedimentation rate (ESR), C-reactive protein (CRP), and IL-6 (markers of inflammation); and 
low-density lipoproteins (LDL; lipid profile) at 3 and 6 months compared to baseline. Change 
in a serum biomarker at 12, 24 and 52 weeks compared to baseline will be reported as sample 
mean along with 95% confidence interval. Myeloma labs will also be tested at 4 and 8 weeks. 
Exploratory Objectives: 
1.  Alterations in epigenetics of T cells and plasma cells secondary to a WFPBD intervention will 
be assessed by metabolism-related chromatin damage (epigenetic changes) in peripheral 
blood T cells (CD4 and CD8) at 12 weeks compared to baseline. Epigenetic changes at 12 
weeks compared to baseline will be reported as sample mean along with 95% confidence 
interval. 
2. Alterations in the fecal microbiome after a WFPBD intervention will be assessed by shifts in 
the fecal microbiome measured by change in diversity and relative abundance of butyrate- 
producing bacteria. Change in microbiome diversity and relative abundance and at 12, 24, and 
52 weeks compared to baseline will be reported as sample mean along with 95% confidence 
interval. 
3. Changes in visceral, subcutaneous and bone marrow fat as determined on PET imaging 
between 6-12 months compared to baseline will be reported as sample means along with 95% 
confidence interval. Pearson correlation with changes in BMI and paraprotein between 24 
weeks and baseline will be reported as well. 
 
15.0 TOXICITIES/RISKS/SIDE EFFECTS 
Toxicity grading will be performed in accordance with NCI CTCAE v5.0. Unanticipated but 
possible side effects of the plant-based meals include: 
• 
Nausea 
• 
Vomiting 
• 
Diarrhea 
• 
Dyspepsia 
• 
Bloating 
15.1 
Serious Adverse Event (SAE) Reporting 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 

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• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
 
Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 
 
SAE reporting is required as soon as the participant starts investigational 
treatment/intervention. SAE reporting is required for 30-days after the participant’s last 
investigational treatment/intervention. Any event that occur after the 30-day period that is 
unexpected and at least possibly related to protocol treatment must be reported. 
 
Please note: Any SAE that occurs prior to the start of investigational treatment/intervention 
and is related to a screening test or procedure (i.e., a screening biopsy) must be reported. 
 
All SAEs must be submitted in PIMS. If an SAE requires submission to the HRPP office per 
IRB SOP RR-408 ‘Reporting of Serious Adverse Events’, the SAE report must be submitted 
within 5 calendar days of the event. All other SAEs must be submitted within 30 calendar 
days of the event. 
The report should contain the following information: 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment(s) 
• 
If the AE was expected 
• 
Detailed text that includes the following 
o An explanation of how the AE was handled 
o A description of the participant’s condition 
o Indication if the participant remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
 
 
16.0 PROTECTION OF HUMAN PARTICIPANTS 
Prior to the enrollment of each participant, the risks, benefits and objectives of the study will 
be reviewed with the participant, including a discussion of the possible toxicities and side 

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effects. Alternative, non-protocol, treatment options will be discussed with the participant. It 
will be reviewed that participation in this clinical trial is voluntary and that the participant may 
withdraw consent at any time. 
Consent process: All patients who meet the inclusion criteria will be eligible. Participation in 
the trial is voluntary. All participants will be required to sign a statement of informed consent, 
which must conform to IRB guidelines. The informed consent procedure is described in 
Section 8.0. 
Potential Risks: Our eligibility criteria and screening procedures are established to exclude 
individuals for whom plant-based diet, blood collection and bone marrow biopsy are not 
appropriate. Our screening procedures begin with medical chart review to identify individuals 
with any condition or reason that may prohibit study entry, followed by oncologist approval to 
screen/identify patients who may not be eligible for any additional reasons. Finally, in-person 
assessments will be performed to screen/identify patients for contraindications to the study. 
This multi-gated comprehensive approach should systematically identify and screen out any 
individual for whom this study is contraindicated. Patients will be responsible for covering the 
cost of treating any research-related injuries. The risks associated with trial participation are 
described in detail in Section 15. 
Bone Marrow Biopsy — Some minor risks are associated with an aspirate and core biopsy 
such as bruising and/or discomfort; however, this procedure is considered to be of minimal 
risk. 
Blood Collection — There are some minor risks associated with a blood draw, e.g. bruising, 
discomfort, however this procedure is considered to be of minimal risk. 
PET scan — A PET scan carries the risk of radiation exposure. In this study, two scans 
(baseline and at 6-12 months) will be completed for each participant enrolled as standard of 
care, and subsequent scans will be done as clinically indicated. 
There are no known risks of the other study-related assessments in this trial. 
Risks of research participation: The greatest risk is release of information from health or 
research records in a way that violates privacy rights. MSK will protect records so that name, 
address, phone number, and any other information that identifies the participant will be kept 
private. It will be stated to the participant that the chance that this information will be given to 
an unauthorized individual without the participant’s permission is very small. 
Benefits: Dietary modification such as plant-based diets have been shown to induce weight 
loss and reduce the risk of cardiovascular disease. 
Collected biospecimens may be of no benefit to participants since neither the participant nor 
the treating physician will be told the specific results of any research tests on the samples. 
Research using blood or tissues in this study could lead to medical and scientific products 
that could improve prevention, diagnosis and treatment of disease. 

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Costs/compensation: Participants will be charged for physician visits, routine laboratory 
tests and radiologic studies required for monitoring their condition. The participants will not 
be billed for any study-related procedures. Participants will be informed that there are no 
plans to provide financial compensation for use of their human biologic specimens, nor are 
there plans for participants to receive money for any new products, tests, and discoveries 
that might come from this research. 
Alternatives: The alternative to this trial would be not to participate in the study and receive 
routine standard of care. 
Confidentiality: Every effort will be made to maintain patient confidentiality. Research and 
hospital records are confidential. Participants’ names and any other identifying information 
will not be used in reports or publications resulting from this study. Other authorized agencies 
and appropriate internal personnel (e.g. qualified monitors from MSK) and external personnel 
(its authorized agents, the FDA, and/or other governmental agencies) may review patient 
records as required. 
Patient safety: Participants are monitored by physicians, oncology nurses and registered 
dietitians who are very familiar with clinical trials. In the case of an adverse reaction, 
immediate medical attention is available. In the evenings and on weekends, we have a 24- 
hour urgent care facility for outpatients. 
Voluntariness of research participation: Taking part in this study is voluntary and 
participants have the right to withdraw at any time. Participation in the study will not impact 
the clinical care patients receive. 
Withdrawal: Participants may also decide at a later date that they do not want identified 
blood and/or tissue samples to be stored for future research. If participants decide to 
withdraw from the study, specimens will not be used in new studies and any remaining 
portions of samples that have not been used for research will be used only for clinical 
purposes or, if requested by the participant, destroyed. When a participant withdraws from 
protocol, the withdrawal request will be documented in CTMS and the system updated 
accordingly. In addition, a note documenting the participant’s withdrawal must be filed in 
his/her EMR. 
16.1 
Privacy 
MSK’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals/entities described in the 
Research Authorization form. A Research Authorization form must be approved by the IRB 
and Privacy Board (IRB/PB). 
The consent indicates that individualized de identified information collected for the purposes 
of this study may be shared with other qualified researchers. Only researchers who have 
received approval from MSK will be allowed to access this information which will not include 

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protected health information, such as the participant’s name, except for dates. It is also 
stated in the Research Authorization that their research data may be shared with others at 
the time of study publication. 
 
16.2 
Data Management 
An MSK Research Regulatory Associate (RRA) and Clinical Research Associate (CRA) will 
be assigned to the study. The RRA and CRA will be supervised by the Clinical Research 
Manager (CRM) and the Principal Investigator in the Myeloma Service. The responsibilities 
of the RRA and CRA include project compliance, data collection, abstraction and entry, data 
reporting, regulatory monitoring, problem resolution and prioritization, and coordinate the 
activities of the protocol study team. Case Report Forms (eCRFs) within an Electronic Data 
Capture (EDC), Medidata. Source documentation will be available to support the 
computerized patient record. The principal investigator will maintain ultimate responsibility for 
the clinical trial. 
Data storage 
The data collected for this study will be entered into a secure database (Medidata) generated 
specifically for this study. MSK’s Medidata application analyst will assist with building the 
database based on provided specifications. Source documentation will be available. 
Final data sets for publication will be locked and stored centrally for potential future access 
requests from outside entities. 
 
16.3 
Regulatory Documentation 
 
Prior to implementing this protocol at MSK, the protocol, informed consent form, HIPAA 
authorization and any other information pertaining to participants must be approved by the 
MSK Institutional Review Board/Privacy Board (IRB/PB). There will be one protocol 
document and each participating site will utilize that document. 
 
Participating sites that are conducting specimen analysis should submit this protocol to their 
IRB according to local guidelines. Copies of any site IRB correspondence should be 
forwarded to MSK. 
 
16.4 
Quality Assurance 
Weekly registration reports will be generated to monitor patient accruals and completeness 
of registration data. Routine data quality reports will be generated to assess missing data 
and inconsistencies. Accrual rates and extent and accuracy of evaluations and follow-up will 
be monitored periodically throughout the study period and potential problems will be brought 
to the attention of the study team for discussion and action. 

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16.5 
Data and Safety Monitoring 
The Data and Safety Monitoring Plan utilized for this study must align with the MSK DSM 
Plan, where applicable. 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan Kettering were approved by 
the National Cancer Institute in August 2018. The plans address the new policies set forth by 
the NCI in the document entitled “Policy of the National Cancer Institute for Data and Safety 
Monitoring of Clinical Trials.” 
There are several different mechanisms by which clinical studies are monitored for data, 
safety and quality. At a departmental/PI level there exists procedures for quality control by 
the research team(s). Institutional processes in place for quality assurance include protocol 
monitoring, compliance and data verification audits, staff education on clinical research QA 
and two institutional committees that are responsible for monitoring the activities of our 
clinical trials programs. The committees: Data and Safety Monitoring Committee (DSMC) for 
Phase I and II clinical trials, and the Data and Safety Monitoring Board (DSMB) for Phase III 
clinical trials, report to the Deputy Physician-In-Chief, Clinical Research. 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required. 
The MSK DSMB monitors phase III trials and the DSMC monitors non-phase III trials. The 
DSMB/C have oversight over the following trials: 
• 
MSK Investigator Initiated Trials (IITs; MSK as sponsor) 
• 
External studies where MSK is the data coordinating center 
• 
Low risk studies identified as requiring DSMB/C review 
The DSMC will initiate review following the enrollment of the first participant/or by the end of 
the year one if no accruals and will continue for the study lifecycle until there are no 
participants under active therapy and the protocol has closed to accrual. The DSMB will 
initiate review once the protocol is open to accrual. 

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IRB Number: 21-135 A(6) 
Approval date: 27-Mar-2024 
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New York, New York 10065 
Page 40 of 45 
 
 
 
 
 
 
 
 
 
 
 
 
 
17.0 
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1275 York Avenue 
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1275 York Avenue 
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Approval date: 27-Mar-2024 
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1275 York Avenue 
New York, New York 10065 
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IRB Number: 21-135 A(6) 
Approval date: 27-Mar-2024 
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New York, New York 10065 
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18.0 
APPENDICES 
Appendix A – EORTC QLQ C30 Survey 
Appendix B – Block Food Frequency Questionnaire 
Appendix C – Dietary Recall Handout (to be sent to patient during screening period) 
Appendix D - Stool Collection Instructions (to be sent to patient during screening period) 
Appendix E – Whole Foods Plant Based Diet Handout (to be sent to patient during screening 
period) 
Appendix F – Sample Plantable Weekly Menu (to be sent to patient during screening period) 
Appendix G – Plantable Sample Menu Ingredients (to be sent to patient during screening 
period) 
Appendix H – Plantable App Screenshots (to be sent to patient during screening period) 
Appendix I – American College of Lifestyle Medicine – WFPBD plate (to be sent to patient 
during screening period) 
Appendix J – American Cancer Society Diet and Activity Guidelines (to be sent to patient 
during screening period) 
Appendix K – Waist Circumference Measurement (to be sent to patient during screening 
period) 
Appendix L – Email Notification for EORTC QOL Survey via MSKEngage 
Appendix M – Email Notification for Block FFQ via MSKEngage 

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-135 A(6) 
Approval date: 27-Mar-2024 
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1275 York Avenue 
New York, New York 10065 
Page 45 of 45 
 
 
Appendix N – Optional Post Intervention Feedback Survey at end of study at 52 weeks