Introduction: Chimeric antigen receptor (CAR) T-cell therapies have radically changed the treatment paradigm of patients (pts.) with relapsed/refractory (r/r) hematologic malignancies. Despite their remarkable efficacy, health care disparities can impact outcomes of pts. in the real-world setting. Living in a disadvantaged neighborhood has been associated with inferior outcomes after allogenic hematopoietic stem cell transplantation (HSCT), independent from individual-level socioeconomic (SE) factors. Our study aimed to identify the impact of neighborhood adversity on survival outcomes of recipients of CAR T-cell therapies, as this has not been yet described. Methods: We retrospectively identified consecutive adult pts. with r/r B-cell non-Hodgkin lymphoma (B-NHL) and multiple myeloma (MM) who received CAR T-cell therapies at our center from May 2018- January 2023. Neighborhood disadvantage was defined by Area Deprivation Index (ADI), a validated tool that allows for ranking of census block groups based on SE domains (income, education, employment, and housing quality) at a national level. The 2021 national ADI percentile ranks (1-100) were obtained for each pt. using the 9-digit zip code of place of residence, with a higher rank corresponding to higher level of disadvantage. We compared overall survival (OS) and progression free survival (PFS) between pts. with high vs. low ADI. We also examined survival outcomes in relation to estimated distance from place of residence to treatment center (DTC). Time dependent outcomes were calculated from date of CAR T infusion. Pts. with B-NHL and MM were analyzed separately. Baseline variables were compared between groups using chi-squared, t-test, and Wilcoxon rank sum tests as appropriate. Survival estimates were calculated with Kaplan-Meier method, and hazard ratios were generated using cox proportional hazards model. Results: CAR T therapy was administered in 124 and 45 pts. with B-NHL and MM, respectively. Median ages were 65 and 62 yrs., 68% and 51% were male, 94% and 84% were White, 47% and 20% had high-risk disease (based on IPI/MIPI for B-NHL, and FISH for MM), 30% and 69% had prior HSCT, and median number of prior therapies were 3 (range 1-6) and 6 (range 4-14), among pts. with B-NHL and MM, respectively. B-NHL subtypes included DLBCL (84%), MCL (6%), FL (5%), and PMBCL (5%), and CAR T products for B-NHL were axi-cel (52%), tisa-cel (24%), liso-cel (18%) and brexu-cel (6%). Ide-cel (82%) and cilta-cel (18%) were used in pts. with MM. We treated pts. from 169 census block groups over 8 states, although 89% pts. were from Ohio. For the entire cohort, median ADI rank was 62.5 (range 1-100) and median DTC was 42.5 (range 1-4559) miles (m). Pts. were categorized (based on median) as having high (> 62.5) or low (≤ 62.5) ADI, and long (> 42.5m) or short (≤ 42.5m) DTC. Longer DTC was significantly associated with higher ADI ( p<0.001). Baseline characteristics (age, sex, prior therapies, prior HSCT, high risk disease, CAR T product) were similar across groups with low vs. high ADI and short vs. long DTC. Median follow up time up was 12 (range 4-60) and 9 (range 4-22) months for living pts. with B-NHL and MM, respectively. For pts. with B-NHL, objective response rates (ORR) (85% vs. 80%; p=0.4), relapse rates (RR) (66% vs. 66%; p=0.9), median OS (19 vs. 14 months; HR of death: 1.2; 95% CI 0.7-1.8; p=0.5) ( Fig.1), and median PFS (10 vs. 5 months, HR of relapse: 1.1, 95% CI 0.7-1.7; p=0.6) were similar for pts. with low vs. high ADI. For pts. with MM, there were no differences in ORR (77% vs. 87%; p=0.3), RR (77% vs. 70%; p=0.5), median OS (14 vs. 18 months; HR of death: 0.8; 95% CI: 0.3-2; p=0.6) ( Fig.2), and median PFS (7 vs. 9 months, HR of relapse: 0.7, 95% CI 0.3-1.4; p=0.3) between those with low vs. high ADI. There were no differences in median OS of pts. with short vs. long DTC for NHL (19 vs. 14 months; HR: 1.2, 95% CI 0.7-1.9, p=0.4) or MM (14 vs. 20 months; HR: 0.9, 95% CI 0.3-2.5; p=0.9), or when DTC was analyzed as a continuous variable. Conclusion: In patients with r/r B-NHL and MM who received CAR T-cell therapies, response rates and survival outcomes were comparable regardless of neighborhood disadvantage level or distance to treatment center. Pts. living in more disadvantaged neighborhoods travelled longer distances for treatment. These findings prompt future investigation into referral patterns and access barriers to cellular immunotherapy, especially in disadvantaged neighborhoods.

PURPOSE Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), two B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). We compare safety, efficacy, and survival among patients with RRMM treated with standard-of-care (SOC) ide-cel or cilta-cel. METHODS Data were from a retrospective chart review of patients with RRMM leukapheresed by December 31, 2022, with the intent to receive SOC ide-cel or cilta-cel at 19 institutions. An inverse probability of treatment weighting (IPTW) approach was used to compare outcomes by therapy type. RESULTS A total of 641 patients were leukapheresed by December 31, 2022, with ide-cel (n = 386) and cilta-cel (n = 255). Five hundred eighty-six patients were infused (n = 350 for ide-cel; n = 236 for cilta-cel) with a median follow-up of 12.6 and 13.0 months for ide-cel and cilta-cel, respectively. After IPTW, patient characteristics were well balanced. Cilta-cel was associated with higher likelihood of grade ≥3 cytokine release syndrome (CRS; odds ratio [OR], 6.80 [95% CI, 2.28 to 20.33]), infections (OR, 2.03 [95% CI, 1.41 to 2.92]), second primary malignancies (OR, 1.77 [95% CI, 0.89 to 3.56]), and delayed neurotoxicity (OR, 20.07 [95% CI, 4.46 to 90.20]). Cilta-cel was also associated with better treatment responses (≥complete response: OR, 2.42 [95% CI, 1.63 to 3.60]), longer progression-free survival (hazard ratio [HR], 0.48 [95% CI, 0.36 to 0.63]), and longer overall survival (HR, 0.67 [95% CI, 0.46 to 0.97]). No associations were observed between therapy type and immune effector cell–associated neurotoxicity syndrome, any CRS, severe cytopenia at days 30 and 90, or nonrelapse mortality. We observed consistent findings when repeating the analyses restricting the ide-cel cohort to patients infused during the same time period as Food and Drug Administration approval for cilta-cel (≥March 2022). CONCLUSION Cilta-cel demonstrated superior efficacy and survival, with higher incidence of certain toxicities, compared with ide-cel.

Data describing outcomes of teclistamab in multiple myeloma patients with prior exposure to BCMA-directed therapy (BCMA-DT) are limited. The goal of this multicenter retrospective analysis was to report the efficacy and safety of standard-of-care teclistamab in patients with prior BCMA-DT. A total of 385 patients were included, of whom 193 (50%) had received prior BCMA-DT, including 47 (24%) patients with prior antibody-drug conjugate (ADC)-only, 99 (51%) with chimeric antigen receptor T-cell therapy (CAR T)-only, 36 (19%) with both ADC and CAR T, 6 (3%) with bispecific antibody-only, and 5 (3%) with other combinations. Most safety parameters between cohorts were comparable. The prior BCMA-DT cohort had a lower overall response rate (ORR: 48.7% versus 61.5%; p = 0.012), and median progression-free survival (PFS: 4.6 versus 8.2 months; p = 0.017) compared to the cohort without prior BCMA-DT. However, in multivariable analysis, despite a clear trend, ultimately receipt of a prior BCMA-DT was not independently associated with ORR or PFS (p = 0.057 and p = 0.1, respectively). No significant differences in PFS were noted when stratifying patients by number of prior BCMA-DTs, types of all prior BCMA-DTs received, type of most recent prior BCMA-DT, or depth of response to most recent BCMA-DT. Using the maximally selected rank statistics method, the optimal cut-off for time from the last BCMA-DT exposure to teclistamab initiation was identified as 8.7 months. Patients with >8.7 months between their last exposure to prior BCMA-DT and teclistamab initiation had a significantly improved median PFS with teclistamab (8.1 months, 95% CI: 4.6-11.7) compared to patients with <8.7 months (2.5 months, 95% CI: 1.1-5.7), p = 0.001. Altogether, our findings support the use of teclistamab as a viable treatment option in patients previously exposed to BCMA-DT.

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), the asymptomatic precursors to multiple myeloma, affect up to 5% of the population over the age of 40. Bone involvement, a myeloma-defining event, represents a major source of morbidity for patients. Key goals for the management of myeloma precursor conditions include (1) identifying patients at the highest risk for progression to MM with bone involvement and (2) differentiating precursor states from active myeloma requiring treatment. Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT with [18F]fluorodeoxyglucose (FDG) have improved sensitivity for the detection of myeloma bone disease compared to traditional skeletal surveys, and such advanced imaging also provides this field with better tools for detecting early signs of progression. Herein, we review the data supporting the use of advanced imaging for both diagnostics and prognostication in myeloma precursor conditions.

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are two chimeric antigen receptor T cell (CAR T) therapies approved for use in patients with relapsed/refractory multiple myeloma (MM). Initially approved for late line MM (>4 prior lines), these were recently approved for use in MM with 1-2 prior lines of therapy in April 2024. As their use outside of the pivotal clinical trials continues to expand, it is important to critically evaluate the safety and efficacy of these therapies. Further, it is important to identify patients that would be most likely to benefit from the use of CAR T in earlier lines of therapy. Cilta-cel was initially studied in the phase-I LEGEND-2 study, followed by CARTITUDE-1 and CARTITUDE-4 trials, demonstrating remarkable efficacy. A recent large real-world study also demonstrated similar efficacy, in a mostly pivotal trial ineligible patient population. Based on these impressive results, cilta-cel is currently being studied in trials for newly diagnosed as well as smoldering multiple myeloma. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are known toxicities of cilta-cel (and other CAR Ts), however movement and cognitive disorders (delayed neurotoxicity) and second primary malignancies are an evolving concern. In this article we discuss safety and efficacy data from existing cilta-cel studies. We propose that all patients with MM who have received ≥4 prior lines of therapy should be considered for CAR T. Earlier line use of CAR T should be restricted to patients with a high-risk disease phenotype (eg, functional high-risk disease). This disease phenotype has historically shown poor outcomes with standard triplet regimens and would be most likely to benefit from earlier use of CAR T: considering the availability of other safe and highly effective therapies, and potential high-risk toxicities of CAR T.

ABSTRACT:Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. Overall, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel, of which 54% would not have met CARTITUDE-1 eligibility criteria. In treated patients (N = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell-associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming cilta-cel (n = 191), 94% and 74%; and conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from cilta-cel, the median progression-free survival (PFS) was not reached, with 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen-targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.

Background/Objectives: Chimeric antigen receptor T-cell therapy (CAR-T) has become a key treatment option for relapsed/refractory multiple myeloma (RRMM), but factors impairing T-cell fitness may diminish efficacy. Our exploratory analysis aimed to evaluate the impact of prior treatment with a selinexor-containing regimen on CAR-T outcomes for RRMM patients. Methods: Data for this retrospective cohort study were sourced from electronic medical records at two US academic centers. Kaplan-Meier estimates assessed duration of response (DOR), progression-free survival (PFS), and overall survival (OS), reported as medians with interquartile ranges (IQRs). Cox proportional hazards regression analyzed factors potentially associated with PFS and OS, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Among 45 patients exposed to selinexor before undergoing BCMA-directed CAR-T, median therapy line numbers for selinexor use and CAR-T were 7 and 9, respectively, with 24.4% receiving selinexor as part of bridging. At median follow-up of 68 months, median PFS and OS post CAR-T were 8.0 (IQR 3.1-39.5) and 35.9 (IQR 14.2-NR) months, respectively. Overall response rate to CAR-T was 89%, with a median DOR of 8.1 months (IQR 2.9-39.0). In our multivariable model, patients who received a selinexor-based regimen in the line of therapy preceding CAR-T showed a trend toward reduced risk of death (HR = 0.08; 95% CI 0.02-0.46) and/or disease progression (HR = 0.40; 95% CI 0.14-1.09). Conclusions: Prior selinexor exposure does not appear to compromise CAR-T outcomes in heavily pretreated RRMM, suggesting potential T-cell sparing. Our findings warrant larger, prospective studies to determine whether preemptive selinexor treatment can optimize CAR-T efficacy.

Background: Teclistamab (Tec) received regulatory approval for the treatment of relapsed refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. The risk of CRS and ICANS with Tec is well established with a manufacturer's recommendation of inpatient observation for 48-hours for CRS/ICANS monitoring after the initial 3 step up doses. There are limited real-world data on the characteristics of and risk factors for CRS and ICANS with Tec. Such data could inform management of Tec patients (pts), including patient selection for inpatient or outpatient step-up dosing. Methods: RRMM pts treated with standard-of-care Tec across 13 U.S. academic institutions were included in this analysis. The follow-up data cutoff was 30 April 2024. CRS and ICANS classification was based on the American Society for Transplantation and Cellular Therapy consensus grading criteria. Multivariable logistic regression models were fitted to estimate the effects of covariates on CRS and ICANS events, with a particular focus on grade ≥2 CRS, any-grade ICANS, and the combination of CRS grade ≥2 and/or any-grade ICANS. Results: 385 pts were included in the analysis, with a median of 6 lines of prior therapy. Median age was 68 years (range 31-92), 88 patients (25% of pts with available data) had ECOG ≥2, and 301 pts (78%) would have been ineligible for MajesTEC-1. 48 (33%) of 145 evaluable pts with a baseline bone marrow (BM) prior to Tec had >50% BM plasma cells, 139 pts (36%) had extramedullary disease (EMD) (either paraskeletal or true-EMD) and 5 pts (1%) had plasma cell leukemia prior to start of Tec. 224 pts (59%) received Tec with an accelerated step-up dosing regimen, defined as having at least one step-up dose interval of ≥ 2 days. 220 pts (57%) developed any-grade CRS [Grade 1: 46% (N=179), grade 2: 10% (N=37), grade 3: 0.8% (N=3), grade 4: 0.3% (N=1)]. Median time to CRS from start of Tec was 3 days (range, 0-15). Fifty-four pts (14%) developed any-grade ICANS [Grade 1: 7% (N=26), Grade 2: 5% (N=18), grade 3: 3% (N=10), grade 4: none]. There were no grade 5 CRS or ICANS events. Median time to onset of ICANS from start of Tec was 4 days (range, 0-25). There was one case of hemophagocytic lymphohistiocytosis in the entire cohort. 38% of pts received tocilizumab and 17% of pts received corticosteroids. In univariate analysis (UVA), baseline platelet <50, triple-class refractory, penta-refractory status, and EMD prior to start of Tec were associated with increased risk for CRS grade ≥2 (p-values <0.1) and incorporated in MVA. Baseline platelet <50, age >60, ECOG ≥2, Hgb <8 g/dL, BM plasma cells >50%, and ferritin or CRP in the upper quartile were associated with increased risk for any-grade ICANS in UVA (p-values <0.1). Baseline platelet <50, ECOG ≥2, Hgb <8 g/dL, BM plasma cells >50%, ferritin or CRP in the upper quartile, and prior BCMA exposure were associated with increased risk of CRS grade ≥2 and/or any-grade ICANS in UVA (p-values <0.1). Accelerated step-up dosing, renal impairment (CrCl < 30 mL/min) and baseline LDH in the upper quartile were not associated with an increased risk of either CRS or ICANS in UVA. Baseline BM plasma cells >50% was excluded from multivariable analysis (MVA) due to high number of missing data, since most pts (62%) did not undergo BM biopsy prior to start of Tec. In MVA, risk factors for CRS grade ≥2 included baseline platelet <50 at the start of Tec treatment (OR: 2.35, 95% CI 1.08-5.08; p=0.03) and penta-refractory disease (OR: 2.48, 95% CI 1.13-5.45; p=0.02). Risk factors for any-grade ICANS included platelet <50 (OR: 4.18, 95% CI 1.88-9.28; p=0.0004), age >60 (OR: 7.54, 95% CI 1.63-34.89; p=0.01) and CRP in the upper quartile (OR: 2.51, 95% CI 1.16-5.43; p=0.02). Risk factors for CRS grade ≥2 and/or any-grade ICANS included platelet <50 (OR: 2.65, 95% CI 1.42-4.94; p=0.002) and ECOG ≥2 (OR: 2.07, 95% CI 1.19-3.61; p=0.01). Conclusions: This real-world analysis of RRMM pts treated with Tec revealed comparable rates CRS and ICANS relative to the MajesTEC-1 study, and these were mostly limited to grade 1/2. MVA demonstrated a significantly higher risk of CRS grade ≥2 and/or any-grade ICANS in pts with baseline platelet <50 and/or ECOG ≥2, the former may reflect BM disease burden. These results may help identify pts who are at higher risk for IEC related toxicities with Tec that would warrant inpatient monitoring during initial step-up dosing. OP, AA, & LF: co-first authors. AG, HCL & JK: co-senior authors

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤3 months after CAR T-cell infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤3 months of infusion (P<0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (P<0.001; median PFS for ≥3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T-cell therapy who may benefit from specific interventions pre and post CAR T-cell therpy to improve outcomes.

Introduction: Triplet therapy with a proteasome inhibitor (PI), immunomodulator (IMiD) and dexamethasone (D) is the standard induction regimen for TE-NDMM. However, as new phase III trials supporting quadruplet therapy incorporating anti-CD38 antibody emerge, there is no clear consensus on induction, consolidation and maintenance therapy (MT). This survey aims to understand the perspective of US hematologists/oncologists (HO) perspective in treating TE-NDMM. Methods: A cohort of experienced US hematologist/oncologists (HO) from both academic institutions and community centers participated in survey aimed at approach to induction, consolidation and maintenance treatments in TE-NDMM. The survey was conducted from May 2024 to July 2024. Respondents were stratified based on their FISH results “high risk”, “standard risk” as well as “no” FISH results, followed by induction, consolidation, MT and Minimal residual disease (MRD) assessment. Choice of induction regimen included VRD, DaraVRD, KRD, DaraKRD, VCD, Dara-VCD, or others. Results: Responses were collected from 37 U.S HO. 22 (59%) affiliated with NCCN/NCI. 17 (46%) sub-specialized in MM, 14(38%) identified as stem cell transplanters, and 20 (54%) were general HO. Respondents averaged 12 years of experience (range: 2-41 years) in treating TE-NDMM. Among high-risk FISH patients, 25 (78%) selected DaraVRD induction, 5 (16%) chose DaraKRD, and 2 (6%) opted for VRD. Of those who selected DaraVRD, 22 (88%) used weekly subcutaneous (SC) bortezomib (V), 18 (72%) administered Lenalidomide (R-25mg) on a d1-d21/28-day cycle, and 13 (52%) used weekly dexamethasone (D) at 40mg. 9 (36%) respondents continued daratumumab (Dara) during post-transplant consolidation. For MT, 10 (40%) selected VR, 5 (20%) chose only R, and 3 (12%) preferred DaraVR. 3(12%) based their MT decisions on bone marrow biopsy (BMBx) and MRD assessment. Among those selected DaraKRD, 4 (80%) used once-weekly Carfilzomib (K) on days 1,8,15 of a 28-day cycle, 5(80%) used R-25mg on a d1-d21/28-cycle, and D was split between 20mg (50%) and 40mg (50%) dosages. For consolidation, 3 (75%) used DaraKRD and 1 (25%) used KRD. For post-transplant MT, 2 (40%) respondents chose KR and 3(60%) selected DaraKR. Among standard-risk FISH patients, 20 (63%) of HO selected DaraVRD induction and 12 (38%) chose VRD. For DaraVRD respondents, 17 (85%) used weekly SC V, 13 (65%) administered R-25mg on a d1-d21/28-day cycle, and 11 (55%) used weekly D-40mg. Only 6 (30%) continued Dara during consolidation. For MT, 16 (80%) respondents used only R, and 3 (15%) based their decisions on BMBx and MRD assessment. When FISH results were unavailable, 27 (73%) selected DaraVRD induction and 10 (27%) chose VRD. Among DaraVRD respondents, 26 (96%) used weekly SC V, 18 (67%) administered R-25mg on a d1-d21/28- cycle, and 17 (63%) used weekly D-40mg. 12 (44%) integrated Dara during consolidation. For MT, 18 (67%) respondents prescribed only R therapy, 2 (7%) chose VR, 2 (7%) chose DVR, and 5 (19%) would repeat BMBx and MRD assessment. Among those who selected VRD alone, 9 (90%) used weekly SC V, R-25mg on d1-d14 and d1-d21 were (50%) each, and 6 (60%) used weekly D-40mg. When FISH results were unavailable, 27 (73%) of HO selected DaraVRD induction and 10 (27%) chose VRD. Among DaraVRD respondents, 26 (96%) used weekly SC V, 18 (67%) administered R 25 mg on a d1-d21/28-cycle, and 17 (63%) used weekly D 40 mg. 12 (44%) continued Dara during consolidation. For MT,18 (67%) respondents prescribed only R therapy, 2 (7%) chose VR, 2 (7%) chose DVR, and 5 (19%) would repeat BMBx and MRD assessment. Among those who selected VRD alone, 9 (90%) used weekly SC V, R-25 mg on d1- d14 (50%) and d1-d21 (50%) and 6 (60%) used weekly D-40 mg. Overall, 79% did not base their maintenance therapy decisions on MRD results. Conclusion: This study highlights substantial differences among US physicians in the induction, post-transplant consolidation, and maintenance management of TE-NDMM. The survey results indicate variability in choice of induction, treatment schedules, modes of administration and dosing compared to large phase III trials. These decisions likely reflect the prior experiences of physicians based on efficacy, toxicity and tolerability. The results from our survey will provide valuable insights that can incorporate the US perspective into future MM clinical trials.

e19521 Background: The venous thromboembolism (VTE) risk is high in newly diagnosed multiple myeloma (NDMM) patients, especially within 6 months of beginning treatment and with the use of immunomodulatory-drug (IMiD)-based regimens. SAVED and IMPEDE VTE scores assess risk and NCCN guidelines recommend their use. Few studies have explored optimal thromboprophylaxis agent by risk category which has led to varied treatment strategies. We share our institutional experience using DOACs vs aspirin in NDMM patients and explore incidence of VTE, utility of SAVED and IMPEDE scores, and patient safety. Methods: We retrospectively analyzed outcomes of NDMM patients aged 18 and above from January 2018 to June 2022. Patients receiving anticoagulation for other indications or unable to safely take aspirin or DOACs were excluded. The primary outcome was incidence of VTE in the first 6 months of treatment. Secondary outcomes included patient and treatment factors contributing to VTE risk, comparison of VTE scoring calculators: SAVED vs IMPEDE VTE, and safety of low dose DOAC therapy. Fisher’s exact and Wilcoxon rank sum tests were used to compare patient characteristics between 6-month VTE status. Results: Of 347 NDMM patients that were included, 21% experienced VTE within 6 months. Of those who took aspirin, 20.2% had 6-month VTE. For DOACs, 21.4% taking apixaban and 21.7% taking rivaroxaban had 6-month VTE. There was no significant difference in VTE rate between DOAC or ASA groups (p=0.90). Patients with SAVED score ≥2 (p<0.0006) or prior VTE history (p<0.0001) had significantly higher 6-month VTE rates . Characteristics including age>80, sex, race, BMI>25, IMPEDE score, presence of high-risk cytogenetics, existing use of aspirin or low molecular weight heparin, or transplant status showed no significant difference in VTE rate. Conclusions: This is one of the largest retrospective studies examining efficacy and safety of DOACs in NDMM. Initial analysis showed no significant difference in 6-month VTE rate between NDMM patients treated with aspirin or DOAC therapy. SAVED score appears to delineate high risk VTE patients vs IMPEDE. Follow-up will assess 12-month, 18-month, and overall VTE rates. Bleeding events and analysis for additional high-risk correlates, such as choice of induction regimen, will be presented. This highlights the need for ongoing trials evaluating risk-assigned thromboprophylaxis in patients with MM. [Table: see text]

Despite the astonishing outcomes after chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory multiple myeloma (RRMM), most patients eventually relapse. There are only limited data available on salvage therapies following relapse after BCMA-directed CAR T-cell therapy. Here, we analyzed outcomes of post-CAR T-cell therapy relapse and impact of different salvage strategies in an international cohort of 139 patients (n = 130 ide-cel, n = 9 cilta-cel), receiving talquetamab (n = 28), teclistamab (n = 37), combinations of immunomodulating drugs (IMiDs), proteasome inhibitors (PIs) or CD38 monoclonal antibodies (n = 43), and others (n = 31). The median time to relapse after CAR T-cell therapy was 5 months, 53% had the extramedullary disease (EMD) at relapse, associated with dismal post-relapse outcome (P = 0.005). Overall response and complete response upon salvage therapies were 79% and 39% for talquetamab, 64% and 32% for teclistamab, 30% and 0% for IMiDs/PIs/CD38, and 26% and 3% for others (P < 0.001). Duration of response, as well as median survival, was significantly improved with bispecific antibodies (P < 0.001, respectively). Bispecific antibodies seemed to overcome the poor prognosis associated with early relapse and EMD, and were independent predictors for improved survival in multivariable analysis. In summary, these results suggest bispecific antibodies as the standard of care for relapse after CAR T-cell therapy for RRMM.

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had >= 50% drop in their initial involved sFLC. At 3 months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (>= VGPR) rate of 40%. At 6 months, ORR was 57.5%, with >= VGPR rate of 49%. The renal response rate at 3 and 6 months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p = 0.006), and achievement of >= VGPR (OR 21.7 p < 0.0001) were significantly associated with renal response. Also, a >= 50% drop in sFLC was favorably associated with renal response (OR 3.39, p = 0.09). With a median follow-up of 36.4 months, the median overall survival (OS) was 11 months. On multivariable analysis, achievement of renal response (hazard ratio [HR] 0.3, p < 0.0001) and newly diagnosed disease (NDMM; HR 0.43, p = 0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab-based regimens had a trend for better OS (p = 0.15), compared to other regimens, but the difference was not significant. At the end of follow-up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab-based therapies showing promise.

Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare. This study utilized the openFDA human drug adverse events (AEs) to analyze global data pertaining to MM patients and patterns of treatment-related AEs. We identified ten most frequently used drugs and drug regimens in six distinct regions, including North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America & the Caribbean (LA). AE patterns were evaluated using the reporting odds ratio combined with a 95% confidence interval. AE reports were more prevalent in men than in women across all regions. Cardiotoxicities were more likely observed in AS and EU, while secondary neoplasms were more frequently reported in the EU. Nephropathies were prominent in OC, AF (in males), and AS (in females), while vascular toxicity, including embolism and thrombosis, was more common in NA (in males). A notable improvement in survival, particularly in AS, EU, and NA, with a significant decline in death rates was observed. Hospitalization rates displayed less variation in AS and EU but exhibited more pronounced fluctuations in AF, LA, and OC. In conclusion, this comprehensive analysis offers valuable insights into the demographic, geographic, and AE patterns of MM patients across the globe.

Teclistamab is a B cell maturation antigen (BCMA)-directed bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase I/II MajesTEC-1 trial. Here we report clinical outcomes with standard-of-care teclistamab in a real-world RRMM population. A total of 106 patients from 5 academic centers who received teclistamab from August 2022 to August 2023 were included in this retrospective analysis, 83% of whom would have been considered ineligible for the MajesTEC-1 trial. All patients were triple-class exposed, 64% were penta-class refractory, and 53% had received prior BCMA-directed therapy. Cytokine release syndrome was observed in 64% of patients, and only 1 event was grade ≥3, whereas immune effector cell-associated neurotoxicity syndrome was observed in 14% of patients (3 events were grade 3 or 4). One-third (31%) of patients experienced at least 1 infection, with nearly half of these infections graded as severe (grade ≥3). The overall response rate (ORR) was 66%, and the complete or better response rate was 29%. The ORR was 47% for patients with extramedullary disease (EMD), 59% for patients with prior BCMA-directed therapy exposure, and 68% for patients with penta-refractory disease. At a median follow-up of 3.8 months, the median progression-free survival (PFS) was 5.4 months (95% CI, 3.4 months to not reached), while median overall survival was not reached. Patients with Eastern Cooperative Oncology Group Performance Status ≥2, EMD, and age ≤70 years had inferior PFS on multivariable analysis. Our study demonstrates reasonable safety and good efficacy of teclistamab in patients with RRMM treated in a real-world setting.

Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.

Therapeutic plasma exchange (TPE) is an extracorporeal technique where patient’s plasma containing pathogenic substances is separated and removed from the whole blood, while the cellular component is returned to the patient mixed with replacement solution via an apheresis machine. Due to its ability to remove pathogenic substances from plasma including immunoglobulins, TPE has proven efficacious in the management of various disorders across different medical disciplines, including plasma cell dyscrasias, which are characterized by the abundant secretion of non-functional immunoglobulins produced by an abnormally proliferating plasma cell clone. This review summarizes the current indications of TPE in plasma cell-related disorders and discusses its application, safety, and therapeutic effects.

BCMA-directed chimeric antigen receptor T-cell (CAR T) therapies, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have transformed the treatment landscape for relapsed-refractory multiple myeloma (RRMM), offering remarkable efficacy with hallmark toxicity risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The FDA mandates a 4-week monitoring period at the treatment center as part of a Risk Evaluation and Mitigation Strategy (REMS) to monitor and manage these toxicities, which, while prudent, may add unnecessary challenges related to access and socioeconomic disparities. We sought to assess CRS and ICANS onset and duration, as well as causes of non-relapse mortality (NRM) in real-world BCMA CAR T recipients in order to better inform future changes to the monitoring guidelines for CAR T recipients. This is a retrospective study across four academic centers that examined 129 ide-cel and cilta-cel recipients that received CAR T cell infusions from May 2021 to June 2023. Infusion and toxicities were managed per institutional guidelines in accordance with previously published guidelines. While differences were noted in the incidence and duration of CRS/ ICANS between ide-cel and cilta-cel, late-onset CRS and ICANS were rare after 2 weeks following infusion (0% and 1.6%, respectively). NRM was driven by hemophagocytic lymphohistiocytosis and infections in the early follow-up period (1.1% until Day 29), then by infections through three months post-infusion (1.2%). Our findings suggest that 25% of patients had to relocate for 4 weeks due to distance from the treatment center. With the low risk of CRS and ICANS after 2 weeks, a flexible shorter monitoring period may be reasonable, emphasizing collaboration with referring oncologists to improve NRM.