bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of response to upfront bortezomib, lenalidomide and dexamethasone (VRd) in multiple myeloma.
Authors: Keruakous Amany , Day Silas , Borogovac Azra , Holter Jennifer L. , Asch Adam Steven , Yuen Carrie 
Published: May 2020

e20507 Background: Achievement of response to less than very good partial response (VGPR) after initial induction is an adverse prognostic factor for progression free survival (PFS) in multiple myeloma (MM). Triplet regimen has been demonstrated to be more effective as compared to doublets, with VRd being the preferred induction regimen in newly diagnosed multiple myeloma (NDMM) based on SWOG077 (43.5% VGPR or better). However, recent studies using quadruple combination, daratumumab-VRd, has shown deep response with 63% reached stringent complete remission (sCR) and CR. Balancing efficacy and toxicity in selecting induction regimen in treatment of MM is a challenge due to advanced age and comorbidity. Biomarkers that guided selection based on prediction for efficacy would be clinically useful. In this study we hypothesized that there is a subgroup of patients with MM that would not benefit from upfront VRd could be identified by biologic factors. Methods: For this retrospective study, we selected a cohort of patients with NDMM who were treated with upfront VRd to be evaluated for response after 3-6 cycles of treatment. We identified variables of risk classification that included cytogenetics, ISS stage, immunoglobulin subtype, light chain restriction, pre-treatment albumin level, bone marrow disease burden, end-organ involvement (hypercalcemia, anemia, renal insufficiency and lytic bone lesions), and presence of extra medullary disease. We analyzed the correlation between variables and response to therapy using Chi Square (Fisher’s Exact) test. Results: Among 175 patients treated in our institution starting April 2011 through May 2018, 120 patients received bortezomib-based regimen with 80% (96 subjects) received VRd and 20% (24 subjects) received Vd, with median age of 60.5 (39-74). After 3-6 cycles of VRd, 50% of patients achieved VGPR or better (48/96), 43% achieved partial response (PR) (43/96), 5% did not respond (5/96). Our data showed that immunoglobulin subtype has statistical significant impact on response to VRd; with increased incidence of VGPR or better in IgA myeloma (79%) as compared to IgG myeloma (37%) (P-Value < 0.0006). In IgG myeloma, we showed increased proportion of patients with PR (56%). Additionally, all 5 patients who did not respond to VRd had IgG myeloma. Other variables did not show statistically significant impact to response to upfront VRd. Conclusions: We conclude that IgG subtype MM predicts suboptimal response with VRd. Thus other regimens or four-drug regimen should be considered for upfront therapy in IgG subtype of MM.
Outcomes of daratumumab, pomalidomide, and dexamethasone (DPd) followed by high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) in patients with relapsed/refractory myeloma RRMM.
Authors: Abdallah Al-Ola A. , Dias Ajoy , Kawsar Hameem I , Mohyuddin Ghulam Rehman , Sigle Monia , Mahmoudjafari Zahra , Shune Leyla Osman , McGuirk Joseph , Ganguly Siddhartha 
Published: May 2020

e20508 Background: The number of therapeutic options for patients with RRMM has increased significantly. Our institute treated a series of patients with induction therapy consisting of DPd followed by HDCT/ASCT. We present the early outcomes of these patients. Methods: We treated 16 patients with RRMM at the University of Kansas Health System between May 2016 and October 2019, with DPd as induction therapy followed by HDCT/ASCT. DPd was administered as Daratumumab 16 mg/kg weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks; pomalidomide was dosed at 4 mg orally on days 1-21 of a 28-day cycle; and dexamethasone 20 or 40 mg weekly. Responses were evaluated using the 2016 International Myeloma Working Group (IMWG) criteria. Results: Patients had received a median of two prior regimens. Out of the 16 patients: 81% received ASCT prior to this treatment. In addition, 75%,81% and 68% were refractory to proteasome inhibitors (PI), immunomodulatory agents (IMiDs), and double refractory to IMiDs and PI, respectively. Median time from diagnosis to treatment was 12 months. Median number of DPd cycles received was 4 cycles. A median follow-up of 27 (9-39) months, the overall response rate (ORR) after induction treatment with DPd was 100%. ORR on day 100 post ASCT was 100%, 65% achieved ≥CR, and 81% achieved ≥VGPR. There was no treatment related mortality on day 100. Median progression free survival was 34 months (95%, CI = NA), median overall survival was not reached. The most common grade ≥ 3 adverse events were thrombocytopenia 53%, anemia 40%, neutropenia 53%. Conclusions: DPd as induction therapy followed by HDCT/ASCT demonstrated deep, durable, and clinically meaningful responses with manageable safety profile in patients with RRMM. [Table: see text]
ISS stage and network risk score to predict benefits of multiple myeloma treatment options.
Authors: Liu Yu , Wang Li , Yu Haocheng , Parekh Samir S. , Schadt Eric , Zhu Jun 
Published: May 2020

e20511 Background: Multiple myeloma (MM) is molecularly heterogeneous with many treatment regimens developed targeting different aspects of the disease. Multi-omics studies are now widely available, facilitating a precision medicine approach for personalized MM treatments. However, data from these studies vary with respect to treatment regimens, patient age, disease stage, and genomic alterations, thus complicating identification of treatment effects. Methods: From a Multiple Myeloma Molecular Causal Network (M3CN) model we previously described, we identified a prognostic subnetwork (prognNET) associated with survivals of newly diagnosed MM (NDMM) patients. We derived a network risk score (NRS) for each patient by inferring their molecular state with respect to prognNET, and partitioned patients into NRS low, medium, and high groups (referred as NRSL/M/H). We validated NRSL/M/H to be significantly associated with progression free survival (PFS) and overall survival (OS) in single variate and multi-variate Cox regression models including age and ISS stage in TT2,3,4 and HOVON studies. Results: To determine the impact of NRS in an independent contemporary dataset, we examined NDMM patients with RNAseq data in the MMRF-CoMMpass study. Among young patients (age < 65), ones with combined therapies (CoTs) as the first line therapy (n = 363) had better survival than ones on proteasome inhibitors (PIs) (n = 93) (p = 0.027 and 0.002 for PFS and OS). When stratified by ISS stage and NRS, there was no significant difference between CoTs and PIs except that in the stage I-NRSL group, patients on PIs had better PFS than ones on CoTs (p = 0.016). This suggests that NRS may be able to discriminate ISS stage I patients that do not need CoT. Similarly, we studied the ability of NRS to discriminate patients that benefit from autologous stem cell transplant (ASCT). In a model combining age, ISS stage, NSR, and induction treatment, ASCT was associated with better survival. When stratified young patients on CoTs by ISS stage and NRS, only the stage II-NRSM and stage III-NRSM patients benefited from ASCT in term of PFS (p = 0.01 and 0.005) and OS (p = 0.004 and 0.04). Conclusions: Stage and NRS group should be considered in personalizing treatment options for NDMM patients.
Cytogenetic abnormalities in MM: Association with disease characteristics and treatment response.
Authors: Abdallah Nadine , Buadi Francis , Greipp Patricia T. , Gertz Morie A. , Kapoor Prashant , Dispenzieri Angela , Baughn Linda , Lacy Martha , Hayman Suzanne R. , Dingli David , Go Ronald S. , Hobbs Miriam A. , Lin Yi , Kourelis Taxiarchis , Siddiqui Mustaqeem Ahmad , Kyle Robert A. , Ketterling Rhett P. , Rajkumar S. Vincent , Bergsagel Leif P. , Kumar Shaji 
Published: May 2020

e20520 Background: Cytogenetic abnormalities detected by FISH are found in the majority of multiple myeloma (MM) patients. Although their prognostic value has been studied extensively, less is known about their association with disease characteristics and treatment response. Methods: To address these questions, we designed a retrospective study including 2031 Mayo Clinic patients diagnosed with MM from 2004 to 2018. We compared baseline characteristics and treatment outcomes between primary cytogenetic groups: t(11;14), t(4;14), t(14;16), (14;20), t(6;14), unknown IgH translocation/del and trisomy (without IgH translocation). These included 373, 177, 78, 20, 18, 228 and 791 patients respectively. Kruskal-Wallis and Fisher’s exact tests were used for categorical and continuous variables respectively. Time to next treatment (TTNT) was estimated using Kaplan-Meier method and compared using Log-Rank test. Results: t(4;14), t(14;16), t(6;14) and t(14;20) groups were associated with hemoglobin < 10 g/dL, beta2microglobulin > 5.5 µg/ml, ISS stage 3 and ≥50% bone marrow plasma cells. The latter 3 groups were also associated with renal dysfunction (Cr ≥2 mg/dL) and higher urinary monoclonal protein. t(4;14) was associated with IgA isotype, serum monoclonal protein ≥1g/dL and plasma cell labeling index ≥1%. Light chain myeloma was more prevalent in patients with t(11;14). Overall response rate (ORR) to proteasome inhibitor (PI) induction was higher for those with IgH translocations (any) compared to trisomies (85% vs 77% P = 0.02), while ORR was higher for those with trisomies with immunomodulatory drug (IMiD) induction (90% vs 78% P < 0.01). The rate of ≥ very good partial response was higher for patients with high risk IgH translocations [t(4;14), t(14;16) or t(14;20)] compared to standard risk with PI-IMiD combination treatment (88% vs 65% P < 0.01). Otherwise, response rates did not differ between these 2 groups. TTNT was longer in patients with trisomies compared to those with IgH translocation with IMiD or PI-IMiD treatments (32.2 vs 19 and 44 vs 27.4 months, respectively P < 0.01). For all cytogenetic groups, better treatment responses and longer TTNT were seen with PI-IMiD combinations compared to other treatments. Conclusions: t(4;14), t(14;16), t(6;14), and t(14;20) are associated with high risk disease characteristics. Patients with IgH translocations may have better response to PI induction compared to those with trisomies, while those with trisomies may have better response to IMiD treatment, with best outcomes for both seen with PI-IMiD combinations.
Assessing the relationship in relapsed-refractory multiple myeloma between response, progression, and survival between pooled clinical trial subjects and a real-world electronic medical record data source.
Authors: Watson Mark Layton , Hurmiz Charlie , Smith Jordan , Marada Suresh , Galaznik Aaron , Diamond Sheila , Fields Bryant , Davi Ruthanna 
Published: May 2020

e20525 Background: Despite new treatments, Relapsed-Refractory Multiple Myeloma (RRMM) remains an incurable disease1. In a recent study by Moreau et al, there was a demonstrated survival benefit to treatment with pomalidomide in RRMM patients2. To better understand how the relationships between initial depth of response and long-term prognosis can inform clinical decision making and guide new compound development, we performed an analysis of standardized clinical trial patient pool data compared with Real-World Data (RWD), across multiple studies. Methods: Pooled clinical trial data was obtained from a Study Data Tabulation Model (SDTM) dataset (n=1,815) from the Medidata Enterprise Data Store. De-identified Oncology EMR data was sourced from the Guardian Research Network™ (GRN)5 of integrated delivery systems from 2010-2018, with robust clinical endpoint extraction and curation to enable outcomes comparisons (n=962). Subject selection was refined based on the inclusion/exclusion criteria from the NIMBUS trial2. Response, Progression-free survival (PFS), and Overall Survival (OS) were extracted. Patients were stratified by age, gender, and prior regimens. Log-rank tests were conducted to compare PFS and OS in patient sub-populations at 90, 180, and 240 days from most recent treatment start. Cox proportional hazard models assessed predictors of survival. Rates were estimated for common adverse events, including leukopenia, neutropenia, and thrombocytopenia. Factors associated with neutropenia were assessed using logistic regression. Results: Within pooled trial and RWD patients, the majority were on regimens with proteasome inhibitors, followed by immunomodulators, and approximately one third on monoclonal antibodies. Within the pooled trial analysis, survival rates were consistent with published literature rates, at ~4 months and ~12 months, respectively. EMR data analysis showed overall longer times to progression with an increased depth of response, with similar associations. Frequency-Factored Time-to-Progression also decreased. Conclusions: The use of SDTM for pooled clinical trial analyses, together with real-world data, can overcome individual trial sample size limitations and biases. Together this approach can expand the range of populations, relative treatment comparisons, and clinical events that can be studied to more comprehensively understand the complexity of the oncology treatment landscape.
Daratumumab (Dara) and hyperfractionated cyclophosphamide (HyperCy)/dexamethasone (Dex) with and without carfilzomib (Car) for the treatment of relapsed/refractory multiple myeloma (RRMM).
Authors: Shank Brandon R. , Primeaux Brian , Horowitz Sandra B. , Yeung Erin K. , Lee Irene Y. , Kaufman Gregory Peter , Lee Hans Chulhee , Manasanch Elisabet Esteve , Patel Krina K. , Orlowski Robert Z. , Weber Donna M. , Thomas Sheeba K. 
Published: May 2020

e20528 Background: RRMM can be associated with high disease burden and/or end organ damage requiring rapid disease control. Our group has previously published data with hyperCy-bortezomib (bor)-doxorubicin-dex (Tabchi et al. 2019) for such patients (pts). Dara, a monoclonal antibody targeting CD38, has limited overlapping toxicities with cytotoxic chemotherapy, making it an attractive partner for hyperCy-dex. We report our retrospective experience of pts treated with dara-hyperCy-dex ± car. Methods: Between 5/2016-8/2019, 53 pts were treated with dara (16 mg/kg IV d1,8,15,22)-hyperCy (300-350 mg/m2 IV q12h x 6-8 doses d1-3/4)-dex (20-40 mg IV/PO d1-4, 8-11, 15-18, 22-23) alone (27 records), or with car (20 mg/m2 IV d1-2, 27-36 mg/m2 IV d8-9, 15-16) (32 records) on 28 day cycles. Pts received growth factor, anti-fungal, anti-bacterial, anti-viral, and peptic ulcer prophylaxis. High-risk MM (HRMM) was defined by t(4;14), t(14;16), and/or del 17p. Response was assessed by International Myeloma Working Group Uniform Criteria. Overall response rate (ORR) and disease control rate (DCR) were defined as ≥ partial response and ≥ stable disease, respectively. Each instance of treatment (tx) started > 60 days from the previous cycle start date was counted as a separate record. Patient characteristics, progression-free survival (PFS) and overall survival (OS) were assessed per pt, based on earliest administration date. Results: Median age of pts was 61 (26-77) years. Median number of prior therapies was 4 (1-18). Previous exposure to both lenalidomide and pomalidomide (93%), both bor and car (83%), and dara (64%) was frequent. HRMM was present in 20/42 evaluable pts. After a median of 1 cycle (1-5), ORR was 63%, with ≥ very good partial response in 24%. DCR was 86%. Median PFS was 4.3 months. Median OS was 9.7 months. Grade 3-4 hematologic toxicities included 66% neutropenia, 66% anemia, and 68% thrombocytopenia. Grade 3-4 non-hematologic toxicities included 42% febrile neutropenia, 19% bacteremia, and 15% pneumonia. Within 60 days of tx, 7 pts underwent autologous stem cell transplant (ASCT), and 7 pts died. Conclusions: Dara-hyperCy-dex ± car demonstrates a high ORR and DCR in heavily treated and HRMM, allowing bridging of some pts to ASCT. High rates of hematologic toxicity and risk of infection are manageable with twice weekly monitoring for transfusion support, as well as early detection and intervention for infections. Rates of end organ damage reversal will be presented.
Intestinal microbiome diversity and clinical outcomes with multiple myeloma: A systematic review.
Authors: Ashraf Aqsa , Nabeel Shaha , Ahmed Zahoor , Farooqui Arafat Ali , Rehman Saif ur , Batool syeda Sabeeka , Shah Zunairah , Faisal Muhammad Salman , Farooqi Muhammad Saad , Akhtar Aisha , Anwer Faiz 
Published: May 2020

e20542 Background: Human gastrointestinal microbiome (GM) plays a role in food digestion, drug metabolism and protection against infections. We systematically reviewed the outcomes for multiple myeloma (MM) patients (pts) and its changes in GM diversity (GMD) with regimen-related toxicities. Methods: After a systematic search of PubMed, Embase, Web of Science, Cochrane, and Clinicaltrials.gov (until 01/12/2020), 9 out of 135 studies met our inclusion criteria. Results: GM changes were studied in 1343 pts. 1070 pts received Autologous (Auto) and 119 pts received Allogeneic (Allo) hematopoietic cell transplantation (HCT). 1. Impact of Induction without HCT: Higher levels of Eubacterium hallii and Faecalibacterium prausnitzii in 16 (MM) minimal residual disease (MRD) –ive pts and lower levels in 18 (MM) MRD +ive pts were noted (Pianko 2019). 2. Impact of HCT and microbiome: 1142 pts (MM = 1011) were studied; day+15 samples showed reduction of Bacteroidetes in Auto-HCT compared with Allo-HCT pts. Pts with graft versus host disease (GVHD) harbored more Firmicutes, Proteobacteria and less Bacteroidetes than pts without GVHD (Chiusolo 2015). Day+30 fecal samples (FS) revealed increase in Proteobacteria, Clostridium difficile and decrease in Firmicutes, Fusarium in FS while oral samples (OrS) showed increase in Firmicutes and decrease in Proteobacteria and Glomerella. Increased gastrointestinal adverse effects (AEs) (40%) correlated with decreased GMD especially in pts with ulcerative oral mucositis (OM) (Alexa 2019, El-Jurdi 2019, Apewokin 2015). At 3 years, Allo-HCT pts with highest GMD manifested least treatment-related mortality (TRM) (9%) and vice versa (Taur 2014). 3. Impact of Post-HCT Lactobacillus Probiotics (LBP) or Antibiotics: Improvement in AEs with LBP was statistically insignificant (Gorshein 2017, Giammarco 2016). Pts showed better clinical outcomes with ciprofloxacin and metronidazole (Cp-M) (n = 68) than Ciprofloxacin (n = 66) alone; i.e. overall survival (49% vs 42%), increased number of FS without anaerobic bacteria (53% vs 23%), GVHD (25% vs 50%), OM (82% vs 92%) (Beelen 1999). Conclusions: Treatment for MM alters microbiome diversity. Increased diversity was associated with fewer gastrointestinal AEs. Improvement in AEs with LBP was statistically insignificant. Post-HCT use of Cp-M showed better overall survival.
Exploring multiple myeloma survivor interest in lifestyle interventions.
Authors: Hodge Allen , Williams Alexis , D'Souza Anita , Sheean Patricia M. , Hari Parameswaran , Dhakal Binod , Flynn Kathryn E , Stolley Melinda 
Published: May 2020

e20558 Background: Multiple Myeloma (MM) is the second most common hematological malignancy in the U.S., with higher rates observed in older adults and African Americans (AA). Given treatment advances, most individuals survive at least 5-10 years, making symptom management important. Many survivors struggle with pain, fatigue and limited physical function, all of which may be improved through lifestyle changes. Due to concerns about safety and patient interest, few efforts have considered such interventions. We report the results of an exploratory study to inform a lifestyle program tailored to the needs of the diverse MM survivor community. Methods: MM survivors at least 100 days post-auto transplant with ECOG status of 0-1 completed validated questionnaires and a qualitative interview assessing quality of life, physical activity patterns, social support and interests for a lifestyle program. Results: We recruited 20 survivors, mean age 70 (7.0) years, 70% women, 40% African American, 75% married, 60% college educated. Eighty-three percent were overweight or obese, mean Godin score was 17.56 (18.1) representing insufficient physical activity and 78% did not engage in resistance training at least twice weekly. PROMIS-29 scores indicated that MM survivors had worse physical function, fatigue and pain interference than the general population. However, they reported less social isolation and more social support (informational, instrumental, emotional, companionship). Qualitative data highlighted barriers to healthy lifestyles including “not knowing what dietary changes to make,” fatigue, and safety concerns related to physical activity. Although 67% reported that their oncology team had discussed lifestyle changes with them, most related minimal guidance was given, leaving them confused and wanting more information. All participants acknowledged the potential benefits of healthy eating and exercise on function, fatigue, pain and mood. Particular interests for a lifestyle program included: 1) focused dietary counseling with recipes and cooking guidance; 2) health coach to motivate, and to model and monitor safe exercise; 3) healthcare provider engagement to address health concerns; and 4) preference for in-person with opportunity for web-based program if unable to attend. Many were interested in joining an advisory group to inform intervention development and survivor engagement. Conclusions: MM survivors emphasized their strong interest in having a program where they could meet other MM survivors, discuss their concerns, but also focus on positive behavior changes.