tbuckley/cabot-search huggingface dataset:
Diagnosis disclosure patterns among patients with plasma cell disorders.
Authors: Maria Malik, Akshay Dalvi, Andriy Derkach, Ana M. Sahagun Sanchez Aldana, Jorge Arturo Hurtado Martínez, Gia Merlo, Jennifer M. Ahlstrom, Jay R. Hydren, Saad Zafar Usmani, Susan Chimonas, Robin Ortiz, Urvi A. Shah
Journal: Journal of Clinical Oncology (2024)

e19536 Background: Disclosing or withholding information relating to a precancer or cancer diagnosis – including plasma cell disorders (PCDs) like monoclonal gammopathy, smoldering myeloma, and multiple myeloma – across social networks may impact how patients cope with their diagnosis and prognosis. The purpose of this survey was to investigate diagnosis disclosure patterns among patients with PCDs and identify areas for interventions that effectively utilize social support to navigate cancer diagnoses. Methods: We invited participants with PCDs to answer a 34 question online survey about their diagnosis disclosure patterns and perceptions on the HealthTree Cure Hub between April and December 2024. De-identified aggregated responses were analyzed. Results: A total of 510 participants responded (84% with cancer and 15% with precancer). Almost all (98%) reported sharing their diagnosis (Table 1). The most frequent primary individuals to share with were a spouse, domestic partner, or significant other (60%) and friend (s) (10%). Common reasons that participants chose to share included expecting support (45%), empowering others/spreading awareness (31%), and feeling in control (29%). Most (79%) participants reported that sharing information (with the individual they shared the most with) had a positive impact in their coping, with only 4% reporting a negative effect. Study limitations include selection bias. Conclusions: Patients with PCDs have a variety of motivations for sharing their diagnosis and generally perceive disclosure among their primary social networks to be beneficial to their coping. Oncologists may promote coping by encouraging disclosure. [Table: see text]
MagnetisMM-30: A phase 1b, open-label study of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma (RRMM).
Authors: Alexander M. Lesokhin, Muhammed Saleem Raza, Jorge Acosta, Patrick Muller, Ashleigh O'Connell, Anne Yver, Carolyn Lou, Gregory Finn
Journal: Journal of Clinical Oncology (2024)

TPS7577 Background: Elranatamab (ELRA) is a humanized B-cell maturation antigen (BCMA)–CD3 bispecific antibody (BsAb). Single-agent ELRA induced deep and durable responses with a manageable safety profile in patients (pts) with RRMM enrolled in the phase 2 registrational MagnetisMM-3 study (NCT04649359; Lesokhin et al, Nat Med 2023). Iberdomide (IBER) is a novel CELMoD[TM] agent that induces enhanced antimyeloma tumoricidal and immunomodulatory activity in pts with RRMM (Lonial et al, Lancet Haematol 2022). While IBER in combination with ELRA has not been evaluated clinically, it may provide additional benefit to pts with RRMM based on the mechanisms of action of this novel combination. Methods: MagnetisMM-30 is a phase 1b, open-label, prospective study evaluating the safety, efficacy, and pharmacokinetics of ELRA in combination with IBER in pts with RRMM. The study has 2 parts: Part 1 for dose-escalation and Part 2, randomized for dose optimization. After 2 step-up priming doses of ELRA, pts will receive subcutaneous ELRA weekly with IBER given daily for 21 days of each 28-day cycle. After ≥6 months (cycles) of treatment, pts with a partial response or better for ≥2 months are eligible for reduced dosing frequency of ELRA. Once the 2 combination dose levels (dose levels A and B) are selected from Part 1 as the recommended phase 2 doses for ELRA and IBER, pts in Part 2 will be randomized 1:1 (stratified by the number of prior lines of therapy [LOTs; 1 vs &gt;1]) to dose levels A and B. Key inclusion criteria are pts aged ≥18 years with a MM diagnosis per IMWG criteria, Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and bone marrow function, and disease relapsed or refractory to the last antimyeloma regimen per IMWG response criteria. Pts who received 2-4 or 1-3 prior LOTs, including ≥1 immunomodulatory drug (IMiD) and ≥1 proteasome inhibitor (PI), are eligible for Parts 1 and 2, respectively. All pts must have received ≥2 consecutive cycles of an IMiD-containing regimen and ≥2 consecutive cycles of a PI or PI-containing regimen. Key exclusion criteria are pts with stem cell transplant ≤12 weeks prior to enrollment; active, uncontrolled infection; prior treatment with BCMA-directed or CD3 redirecting therapy or prior CELMoD agents (ie, IBER or mezigdomide). This study is ongoing; Part 1 and Part 2 will enroll approximately 27 and 60 pts, respectively. Study endpoints are listed in the table. Clinical trial information: NCT06215118 . [Table: see text]
Prognostic factors for progression of MGUS including immune phenotype.
Authors: Sawyer Bawek, Janine Joseph, Alan Hutson, Sarah Parker, Joseph Tario, Jens Hillengass
Journal: Journal of Clinical Oncology (2024)

e19537 Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a benign precursor of multiple myeloma (MM). Individuals with MGUS have an overall 1% risk per year of disease progression to active MM or other cancers, although risk varies depending on multiple factors. Natural killer (NK) cells, cytotoxic CD8+ T cells, and dendritic cells have been shown to be altered in MM. Immune profile analysis can help to understand the microenvironment for monoclonal plasma cells better and help identify early factors for progression of MGUS into MM. Methods: We conducted a retrospective review of individuals from 2007-2023 who had a confirmed MGUS diagnosis and available flow-cytometry based immunophenotyping of peripheral blood. Demographics, Charlson Comorbidity Index (CCI), immunoglobulin subtype, date of diagnosis and progression, CD4/CD8 T-cell ratio, CD19+ B-cells, memory B-cells, gamma delta T cells, NK cells, and exhausted/non-exhausted CD4+ and CD8+ T cells were characterized. Descriptive statistics were expressed as means and standard deviations for continuous variables and tabulated frequencies for categorical variables. Pearson’s chi-square test of independence was used to explore the relationship between categorical race and diagnosis across categorical variables. Analysis of variance was utilized to assess the variation in continuous variables by race and diagnosis. The investigation of overall survival (OS) and progression-free survival (PFS) involved using univariate and multivariate Cox models across all pertinent variables. Hazard ratios (HRs) were estimated. A stepwise regression model was incorporated into the Cox multivariate model for a comprehensive analysis. All statistical tests were tested at alpha=0.05. Results: This retrospective study analyzed 151 patients, 84 (55.6%) being male. Average age was 55-77.8 years. The primary sub-diagnosis included IgG kappa at 30.5%, followed by IgG lambda at 29.8%. No significant associations were observed between MGUS subtype and comorbidities, race and Immunoglobulin subtype, Mayo risk status, and free light chain ratio (FLCR). After median follow-up of 666 days, median PFS was 8.07 years with a 95% CI of (4.45, 14.68), and median OS exceeded 12.71 years. The Univariate model for PFS identified the CCI Score (p=0.003, HR=1.25), FLCR (p=0.012, HR=1.024), and NK T-cells (%gated) (p=0.0211, HR=1.033) as significant factors. Only the CCI score was retained in the multivariate stepwise model. Univariate model for OS revealed associations with CCI (p&lt;0.001, HR=1.50), NK T-cells (%gated) (p=0.007, HR=1.05), monoclonal protein (p=0.008, HR=2.80), Non-exhausted T-cells-CD4 (% of CD4 + ) (p=0.013, HR=0.96), and age (p=0.023, HR=1.09). Conclusions: In this single-center retrospective review, only CCI remained prognostically significant in the multivariate model. CCI and NK T-cells were prognostically significant for OS in the univariate analysis.
Mortality trends (1999-2022) in patients with multiple myeloma with pneumonia, influenza, and COVID-19.
Authors: Eli Zolotov, Harsh Parmar, Palka Anand, Josh Zenreich, Adolfo Aleman, Pooja Phull, David H. Vesole, David Samuel DiCapua Siegel, Noa Biran
Journal: Journal of Clinical Oncology (2024)

7553 Background: Patients (pts) with multiple myeloma (MM) are immunosuppressed either due to the hypogammaglobulinemia and impaired plasma cell function or due to pharmacological management and stem cell transplantations. Consequently, they are at a higher risk of infections. This study aims to evaluate the changes in mortality from COVID-19 (CVD), influenza virus (FLU), and pneumonia (PNA) in MM pts in the era of CVD pandemic. Methods: Using the Wide-ranging Online Data for Epidemiologic Research (WONDER) database from the CDC, we collected mortality data for pts with CVD (U07.1 code), FLU and PNA (J09-J18 codes), and MM (C90.0 code). Using sex and ethnicity-specific stratification, the gathered data made it easier to calculate age-adjusted mortality rates (AAMRs) per 100,000 people. Using the collected data we were able to analyze mortality patterns over the years 1999-2022. Results: Overall, 25,271 MM pts died from CVD, FLU and PNA between 1999 to 2022. The mortality rate remained stable from 1999 to 2019 ranging between 0.4 AAMR per 100,000 to 0.3 AAMR, representing an annual percentage change (APC) of -0.5%. However, the mortality rate increased in 2019, rising from 0.3 AAMR per 100,000 to 0.5 in 2022, with APC of 7%. When evaluating the trends by gender, there was an increase in mortality among male pts, rising from 0.4 AAMR per 100,000 to 0.7 between 2019 and 2020, while the increase among females was minimal, from 0.3 AAMR per 100,000 to 0.4. While Hispanic, White, and African American ethnicities mortality increased in 2020-2022, Asian pts maintained a rate of 0.2 AAMR in 2019, 2020, and 2022 (Table). Conclusions: We showed an increase in mortality among pts with MM combined with CVD, FLU, or PNA between 2020 and 2021. It might be attributable to the CVD pandemic, announced by WHO in March 2020. Despite the FDA's approval of the first CVD vaccine in December 2020, the emergence of new CVD variants and limited vaccine availability could have contributed to a continued increase in mortality in 2021.In 2022, we noticed a drop in mortality. It might be explained by the wider accessibility to CVD vaccination or to diminished virulence. Additionally, increased awareness of the importance of CVD vaccinations in immunocompromised pts could also lead to increased FLU vaccination rates. It might explain the downtrending mortality of pts with MM, FLU and PNA only in 2021. This is the first study presenting the mortality trend of MM pts with FLU, PNA and CVD, and comes to highlight the importance of vaccination in immunocompromised MM pts. [Table: see text]
Incidence of infections in clinical trials of treatments for relapsed/refractory multiple myeloma: Systematic review and meta-analysis.
Authors: Omonefe O Omofuma, Yue Zhang, Christian Hampp, Alexander Breskin, Martha Makaratzi, Saager Parmar, Glenn Scott Kroog, Karen Rodriguez-Lorenc
Journal: Journal of Clinical Oncology (2024)

e19517 Background: Although immunotherapy shows favorable survival outcomes among heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients, infections are a common cause of morbidity and mortality that are not well characterized in this patient population. The goal of this study was to estimate the incidence of infections from clinical trials of treatments for RRMM by grade, infection type, and treatment received. Methods: We conducted a literature search in EMBASE, PubMed, Cochrane, approval packages and labeling, and conference proceedings to identify phase 2-3 clinical trials of single drug interventions published prior to 18 June 2023 with data on infections. We included studies of patients aged ≥18 years who received prior MM treatment with an immunomodulatory agent, protease inhibitor, and anti-CD38 antibody. A Bayesian meta-analysis accounting for left-censored data was used to estimate the pooled incidence of infection from the studies by infection type (upper respiratory tract infection [uRTI], sepsis, bacteremia, pneumonia, SARS-COV-2, and bacterial and viral infections), grade (all, grades ≥3, and 5/fatal) and type of treatment received (antibody and CAR-T). Results: Nine studies (7 phase 2, 1 phase 3 and 1 product label) of seven compounds (1 selective inhibitor of nuclear export, 2 CAR-T, and 4 monoclonal and bispecific antibodies) were identified and are/were approved in the US for RRMM treatment. All included articles were published after July 2019 on treatments approved since 2020 for patients who had received ≥4 prior lines of therapy. They included a total of 1,141 patients (median follow-up 10.1 - 23 months). The pooled incidence of all infections was 61.6% (95% credible interval, 58.6%-64.6%), 28.7% (24.7%-32.2%) and 4.1% (2.9%-5.6%) for all-grades, grades ≥3, and 5 respectively. uRTI was the most common type of all-grade infection (22.8% [20.0%-25.6%]) while SARS-COV-2 (6.8% [4.9%-9.4%]) and pneumonia (6.8% [5.0%-9.1%]) were the most common grade ≥3 infections. Sepsis was the most common fatal infection (1.0% [0.4%-1.8%]). Patients treated with monoclonal/bispecific antibodies had a slightly higher incidence of all-grade infections (64.2% [60.4%-67.9%]) compared to CAR-T (58.6% [52.8%-64.2%]). The incidences for these treatments were similar for grades ≥3 (28.9% vs 28.2%) and 5 (3.5% vs 4.5%) infections. Conclusions: In clinical trials of treatment for triple class exposed RRMM, the incidence of infection was high, including grade 3 or higher infections. A large proportion of grade ≥3 infections were attributable to SARS-COV-2 and pneumonia, with sepsis as the most common fatal infection. The incidence of grade ≥3 infection was generally consistent for CAR-T and monoclonal/bispecific antibody therapy.
Gender disparities in Waldenstrom macroglobulinemia: Insights from a comprehensive analysis.
Authors: David Kaldas, Shrinjaya Thapa, Bushra Shariff, Shrikar Modukuri, Kenneth H. Shain, Brandon Jamaal Blue, Julio C. Chavez, Rachid C. Baz, Ariel Felipe Grajales-Cruz
Journal: Journal of Clinical Oncology (2024)

e19064 Background: Waldenstrom Macroglobulinemia (WM) is a rare, complex hematological malignancy with paucity of research about the landscape of gender disparities regarding clinical phenotype, genotype and outcomes. The aim of our abstract to identify those gender-based variations in WM. Methods: This is a retrospective study using a large WM database at Moffitt Cancer Center (MCC). We reviewed the baseline characteristics and molecular information of patients evaluated at MCC from years 1995 to 2020 and outcomes based on gender. Chi-square tests were used for comparing categorical variables and t-test for continuous variables. Kaplan-Meier method was used to compare survival. Results: Total of 265 patients with WM were identified, 63% (167) were males and 37% (98) were females. Mean age at diagnosis was 76 years for both groups, most of the patients were white non-Hispanics (94% in men vs 96% in women) (P=0.09) and had performance status (PS) 0 at diagnosis, 63% in men, 70% in women. The table summarizes baseline characteristics based on gender, men had slightly lower hemoglobin mean 11.1 vs11.5 in women (P =0.013), lower platelet count mean 209 vs 264 in women (P=&lt;0.001) and slightly lower albumin mean 3.8 vs 3.92 in women (P=0.0445). Hyperviscosity and plasmapheresis were more in women 10% vs 2% in men (P=&lt;0.001), Cryoglobulinemia was more in men 11% vs 1% (P=&lt;0.001). There were no statically significant gender differences based on the presence of mutations in MYD88, CXCR4, tp53, or del6q. The median overall survival (mOS) was slightly longer in lower-risk WM female pts, but not in high-risk (based on International Prognostic Scoring System for WM). The overall mOS was 98 months (mo) for females compared to 95 for males, P=0.004. The mOS for low-risk WM was 137 vs 132 mo, for intermediate risk 89 vs 87 mo, and for high-risk 37 vs 39 mo respectively for females and males (P=&lt;0.001). The rate of Diffuse Large B Cell Lymphoma transformation was not different (7% and 4%, respectively for women and men, (P=0.11) Women were more likely to respond to Bendamustine + Rituximab (BR)/BR + steroids than men (43%vs 25%, p=0.04)There were no differences in response to Cytoxan+ Rituximab+ Prednisone, Bruton’s tyrosine kinase inhibitors, or Venetoclax treatment. Conclusions: This retrospective review of a large database of WM patients highlights important gender differences in clinical WM disease features. Women had better overall survival, mainly in lower risk WM and higher responses to immunosuppressive therapy. Although disparities in WM may be multifactorial, disparities based on gender needs more studies to be explored for better understanding of the disease biology and outcomes. [Table: see text]
Improving clinical outcomes in multiple myeloma: Weight maintenance strategies to reduce complications during autologous hematopoietic transplantation.
Authors: Anvay Shah, Danielle Bradshaw, Vishrut Shah, Mark Dalgetty, Sruthi Athota, Faizan Boghani, Michael Stokes, Zachery Branham, Mohammad Mian, Amany R. Keruakous, Ayushi Chauhan, Jorge E. Cortes, Locke Johnson Bryan, Anand P. Jillella, Vamsi Kota
Journal: Journal of Clinical Oncology (2024)

e19533 Background: Multiple myeloma (MM) is the second most prevalent hematological disease. The introduction of melphalan as high-dose therapy followed by autologous hematopoietic cell transplantation (HDT/ASCT) for younger patients has dramatically changed treatment outcomes. Monitoring daily weights has been well documented in Acute promyelocytic leukemia (APL) induction, though little has been documented in myeloma patients receiving ASCT. Monitoring daily weights can be a useful tool in maintaining patients' euvolemic status and can help to facilitate appropriate resuscitation of patients who are otherwise prone to sepsis and fluid overload. At our center over the last few years, we have standardized an approach to monitoring and maintaining the weights of MM patients at or near their pre-admission level with fluids and diuresis, as needed. We report outcomes of weight monitoring on morbidity and mortality during ASCT for MM. Methods: We conducted a retrospective chart review of MM patients receiving ASCT at our center between January 2019 and December 2022. Patients whose weights were monitored and maintained within 3 kilograms of admission weight were identified. We looked at the length of stay (LOS) and ICU transfers during this time. We reviewed the records of 205 patients induced at our center. Results: The mean age was 62 years at the time of transplant (34-78). 119 of the 205 patients identified as men (58%). Out of 205 patients, 152 patients did not have their weights maintained. Of these 152 patients, 7 were transferred to ICU. 53 patients had weights maintained, of which 1 patient was transferred to ICU (OR 0.089 (95% CI 0.018-0.6725) (p = 0.019)). The mean LOS for all patients was 12.97 days. Mean LOS was 12.41(n = 53) and 13.18(n = 152) days for patients whose weights were and were not followed, respectively (mean difference of 0.77 days) (95 % CI of -0.15 to 1.68) (p = 0.0992). 3 of the 205 patients died during admission. In these patients, weights were not maintained before ICU transfer. (OR = 0.4072 (0.0207-8.0136) (p = 0.55)). Conclusions: Fluid overload and sepsis are significant concerns in the treatment of MM. Our findings suggest that maintaining euvolemia can effectively manage patients on the floor and limit and in some cases prevent ICU transfers. Although there are limitations to our study due to its retrospective, single-center nature, the cost-effectiveness and noninvasive means of maintaining euvolemic status support its potential application to standard treatment protocols. Further prospective studies are warranted to validate these findings. [Table: see text]
Population attributable fractions for risk factors for the progression of monoclonal gammopathy of undetermined significance to multiple myeloma in the Veteran population.
Authors: Mei Wang, Mengmeng Ji, Martin W. Schoen, Kristen Marie Sanfilippo, Theodore Seth Thomas, Su-Hsin Chang
Journal: Journal of Clinical Oncology (2024)

7552 Background: Multiple myeloma (MM) is the most common type of plasma cell cancer in the U.S. MM is consistently proceeded by monoclonal gammopathy of undetermined significance (MGUS). Studies have identified several risk factors for the progression of MGUS to MM. However, the contribution of each of these risk factors has not been quantified. We computed the population attributable fractions (PAFs) for selected risk factors in the U.S. Veterans Health Administration (VHA) health system. Methods: Veterans diagnosed with MGUS from 1999-2021 were identified and confirmed via a published natural language processing (NLP) model. We included Black and White patients whose immunoglobulin (Ig) subtype was IgA, IgG, or light chain. Patients who progressed to MM ≤6 months after MGUS diagnosis were excluded. We fit a multivariable time-to-event model controlling for sex, race (Black, White), Ig subtype (IgA, IgG, light chain), agent orange (AO) exposure, as well as M-protein level (≤, &gt;1.5 g/dL), Charlson Comorbidity Index (CCI), obesity status (underweight, normal weight, overweight, obese), and age, all at MGUS diagnosis. The outcome was progression of MGUS to MM, which was also confirmed by a published NLP model. PAF for a risk factor is the fraction of all MM cases in the veteran population that is attributable to this specific risk factor. It accounts for both the prevalence and relative risk of this factor in the population. We calculated PAF for black race, IgA, AO exposure, and overweight/obesity. Results: The analysis included 24,917 patients with MGUS. Among them, 7.8% (n=1,944) progressed to MM (follow-up median 5.6, IQR 3.3-8.8 years). In the veteran population with MGUS, 17.9% of all MM cases was attributable to overweight or obesity (PAF 17.9%, 95% confidence interval [CI] 11.0-24.3%); 7.6% was attributable to black race (PAF 7.6%, 95% CI 4.3-10.9%), 5.7% was attributable to IgA (PAF 5.7%, 95% CI 4.0-7.4%), and 2.4% was attributable to AO exposure (PAF 2.4%, 95% CI 1.0-3.9%). Conclusions: In the veteran population with MGUS, overweight/obesity, the only modifiable factor, is the top contributor to progression to MM cases. In veterans with MGUS, had the overweight or obese MGUS patients to be reversed to normal weight, an estimated 17.9% of the progression cases could have been avoided.Our findings highlight the importance of maintaining a normal weight for reducing the risk of progression of MGUS to MM. [Table: see text]