Richard, Shambavi

Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (≥5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P<0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.

Abstract Patients with multiple myeloma have an elevated risk of severe complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) infection. To demonstrate proof of concept for a pandemic preparedness and response network, the American Society of Hematology Research Collaborative Multiple Myeloma Program developed a prospective, decentralized study within a site-based provider network. In the COVID-19 outcomes in myeloma and the impact of vaccines (COSMIC) study, patients provided consent, permitted electronic health record data collection, completed patient-reported outcomes at baseline, day 30, and day 180 through an electronic study portal, and were compensated for participation. Clinicians at participating sites facilitated study recruitment and shared best practices monthly to accelerate study execution. The COSMIC study rapidly consented 201 patients from 8 participating sites over 4 months (22 January 2024 through 17 May 2024). Consented participants were 30 to 93 years old, with a median age of 67; 46% were female, 69% were non-Hispanic White, 17% were non-Hispanic Black, and 8% were Hispanic/Latino. Patient-reported data completion was 97% at baseline, 81% at 1 month, and 79% at 6 months. At baseline, 55% of patients reported a history of COVID-19 infection and had received a median of 4 SARS-CoV-2 vaccines. For all patients, there were an additional 18 COVID-19 infections and 57 vaccines received during the 6-month observation period. There were no significant differences in health-related quality of life over time or by history of COVID-19 infection. COSMIC demonstrates the feasibility of an innovative evidence generation strategy to drive rapid accrual of patients to address an evolving area of need. This trial was registered at www.clinicaltrials.gov as #NCT05831787.

Abstract Background: Treatment of multiple myeloma (MM) has advanced dramatically over the past decade with median overall survival (OS) for newly diagnosed MM patients (pts) now exceeding 10 years. However, outcomes in pts with high-risk disease remain poor. While most pts with high-risk disease are identified through baseline cytogenetic risk stratification, presence of extramedullary disease, or R-ISS stage, there is also a population of pts who may or may not have these traditional high-risk factors who relapse earlier than expected and have similarly poor outcomes. These pts are often delineated as “functional high-risk,” but a standardized definition of this population in the era of modern myeloma therapy is lacking. Methods: Using the ASH Research Collaborative (ASH RC) Data Hub, we retrospectively searched 7,249 pts across 10 participating institutions for those with newly diagnosed multiple myeloma (NDMM) treated with a triplet or quadruplet induction regimen (with or without autologous stem cell transplant) who had response data available. We evaluated duration of response from first line therapy (PD1) on post-PD1 clinical outcomes such as: time to next treatment (TTNT), time to subsequent progression and/or death (PFS2), and OS. We also analyzed characteristics of those who did vs. did not progress at prespecified time points of interest (12-, 18-, 24-, and 36-months) from the start of induction. We utilized recursive partitioning analyses to iteratively explore all possible cutpoints and identify which one(s) provide the greatest differentiation in the risk of subsequent progression and/or death. Results: We identified 1,305 pts who met the eligibility criteria. Of these, 264 had PD1 data including 201 who had response follow-up (f/u) after PD1. Median f/u after PD1 in this population was 3.2 years, and median PFS2 f/u after PD1 (n=201) was 4.4 years. Months to PD1 was significantly associated with PFS2 (p=0.038). All prespecified time points examined showed inferior PFS2 compared to those with PD1 >36 mos, although each subgroup was not statistically significant, likely due to limited numbers in each group: PD1 <12 mos HR=1.44 (n=43; 95% CI: 0.90 – 2.30; p=0.126), PD1 12-24 mos HR=1.65 (n=30; 95% CI: 0.95 – 2.85; p=0.073), and PD1 24-36 mos HR=1.58 (n=52; 95% CI: 0.98 – 2.53; p=0.059). Similarly, timing of PD1 was also associated with OS post-PD1; pts with PD1 <12 mos had significantly lower OS compared to those with PD1 >36 mos (HR=2.35, 95% CI: 1.27 – 4.32; p=0.006). Our recursive partitioning analysis identified 30-months at the cutoff that produced the greatest differential in outcomes between those above vs. below the landmark. Approximately 23% of the pts analyzed had PD1 within 30 mos, and these pts had significantly lower OS compared to those with PD1 ≥30 mos (HR=1.99, 95% CI: 1.21 – 3.27; p=0.006). Similarly, pts who progressed within 30 mos of starting 1L therapy (n=98) had significantly shorter PFS2 (median=12.5 mos vs 22.8 mos; HR=1.55, 95% CI: 1.09 – 2.20; p=0.014) than those who did not (n=103). Those pts who progressed within 30 mos were more likely to have a higher R-ISS stage at diagnosis (p=0.048), but were not more likely to have high-risk cytogenetics (p=0.66) compared to pts with PD1 ≥30 mos. Interestingly, receiving SCT as part of 1L therapy was not significantly associated with improved PFS2 (HR=0.89, 95% CI: 0.62 – 1.29; 0.54) but was significantly associated with improved OS (HR=0.53, 95% CI: 0.31 – 0.90; 0.018) by univariate analysis. Conclusion: Our study is the first to use a large, multicenter, cohort to evaluate the definition of functional high-risk MM in the era of novel induction therapies. Our data suggest that pts who progress within 30 mos of induction on triplet or quadruplet regimens (irrespective of whether they underwent stem cell transplant) have poorer outcomes than those who progress at 30 mos or later, and that progression prior to 30 mos represents functional high-risk disease. These pts represent a clear unmet medical need, and additional focus should be taken to identify them early with the goal of designing trials to optimize their subsequent therapies.

Abstract Introduction: Multiple myeloma (MM) accounts for nearly 20% of all hematologic cancers in the US and remains a substantial clinical burden, with patients (pts) requiring multiple lines of therapy (LOT). While advances such as BCMA-directed CAR T-cell therapy have improved outcomes, challenges persist, including disease relapse, treatment toxicities (CRS, ICANS, and non-ICANS neurotoxicities), and access. AZD0120 (formerly GC012F) is a first-in-class autologous BCMA/CD19 dual-targeting CAR T-cell therapy using the FasTCAR rapid manufacturing platform that preserves the naive and central memory T-cell phenotypes with marked in vivo proliferative capacity. Phase 1 investigator-initiated trials in China demonstrated deep, durable responses and a favorable safety profile following single-infusion AZD0120 in newly diagnosed and relapsed/refractory MM (RRMM) (Du J, et al. EHA 2024 and ASCO 2023). Here, we report for the first time preliminary phase 1b results from DURGA-1, an ongoing phase 1b/2 clinical trial evaluating the safety and efficacy of AZD0120 in pts with RRMM. Methods: This open-label, single-arm, US-based, multicenter study (NCT05850234) evaluated the safety/tolerability of 2 dose levels (DL) of AZD0120 in pts with RRMM along with preliminary efficacy. Eligible ptswere aged ≥18 y with RRMM (3+ prior LOT [pLOT] including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody), ECOG PS 0–1, and documented evidence of progressive disease. Exposure to BCMA-directed therapy ≥6 mo with best response of PR or better was permitted. Pts underwent lymphodepletion followed by a single infusion of AZD0120. Pts in DL1 received 1x105 cells/kg; DL2 received 3x105 cells/kg. Dose escalation and recommended phase 2 dose (RP2D) were determined by a safety review committee. Phase 1b primary objectives included safety/tolerability and RP2D determination; secondary objectives included efficacy, cellular kinetics (CK), and pharmacodynamics. Results: As of data cutoff (DCO) on 18 July 2025, a total of 25 pts received infusion of AZD0120 (n=12 DL1; n=13 DL2). The median age was 64 y (range 44–78), median pLOT was 4 (range 3–7), 72% were triple-class refractory, 20% had prior BCMA CAR T-cell therapy, 4% had prior teclistamab, 28% had high-risk cytogenetic features [del(13q), del(17p13), t(4;14), t(14;16), amp(1q)], and 8% had extramedullary plasmacytomas. The median time from apheresis to release was 14 d (range 10–30). Median time from apheresis to infusion was 28 d (range 19–44) with 5 pts receiving bridging therapy. Median follow-up was 1.4 mo (range 0–19.3). No dose-limiting toxicities were reported for either dose. The most common treatment-emergent AEs (TEAEs, any grade) were CRS (64%), neutrophil count decreased (56%), and anemia (32%). The most common grade ≥3 TEAEs were neutrophil count decreased (52%), lymphocyte count decreased (32%), and white blood cell count decreased (32%). CRS was reported in 75% of pts at DL1 (all grade 1) and 54% at DL2 (46% grade 1; 8% grade 2), with no cases of grade ≥3 CRS. Median time to CRS onset (DL1/DL2) was 9 d (range 2–11), with a median duration of 2 d (range 1–4); 12 pts (48%) received tocilizumab for CRS management and 12% received dexamethasone. No cases of ICANS, related non-ICANS neurotoxicity, IEC-colitis, or secondary primary malignancies have been reported. There have been no deaths. For efficacy-evaluable patients (n=15), ORR was 100% (33% sCR, 47% VGPR, 20% PR). CR rates in evaluable pts were 30% in DL1 (n=10) and 40% in DL2 (n=5); median time to response was 0.9 mo for both DLs (range 0.9–1.9 DL1; 0.6–1.8 DL2). All MRD-evaluable pts (n=5 DL1; n=3 DL2; DCO 01 July 2025) were MRD-negative by NGS at a sensitivity of 10-5. Three pts in DL1 with ≥12 mo follow-up maintained MRD negativity. Consistent with robust in vivo expansion, CK analysis from 16 evaluable pts (DCO 12 June 2025) demonstrated a median Tmax of 13 d post-infusion with a median Cmax of 85,266 copies/mg gDNA. Median persistence was 42 d (range 13–273). Updated clinical data with additional follow-up will be presented. Conclusion: Preliminary phase 1b results demonstrated AZD0120 was well tolerated, with a low incidence of serious AEs, no grade ≥3 CRS, and no ICANS. FasTCAR-manufactured AZD0120 had expectedin vivo expansion, which may have resulted in the predictable CRS profile. A single infusion of AZD0120 achieved early, deep responses with 100% MRD negativity from 4L+ triple-class‒exposed pts with RRMM.

Abstract Background: Prolonged cytopenias are a well-recognized complication following CAR-T therapy, leading to increased morbidity and healthcare utilization. Autologous SCB offers a potential strategy to promote hematologic recovery. We conducted a retrospective multi-institutional analysis across 18 centers comparing outcomes of SCB versus supportive care alone in RRMM patients who experienced prolonged cytopenias >30 days after CAR-T infusion. Methods: Patients were included if they received SCB within 1 year after commercial CAR-T between 6/2021 and 3/2024. To identify matched controls, we reviewed other CAR-T recipients from the same consortium and selected those with an absolute neutrophil count (ANC) of <0.72x109/L and platelet count of <21K at day 30 post-infusion-thresholds representing the 75th percentile of cytopenia severity in the SCB cohort. These criteria ensured control patients had comparable hematologic toxicity but without SCB. Hematologic recovery in the SCB cohort was assessed using the CIBMTR engraftment criteria. For the non-SCB (nSCB) group, cell counts were analyzed cross-sectionally at day 90 post-CAR-T and compared to the SCB cohort with Kruskal Wallis tests. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan Meier methods. Results: Of the 590 CAR-T recipients, 91 patients (15.4%) developed prolonged cytopenias; 39 patients received SCB and 52 did not. SCB patients more frequently had ISS stage III disease (23.1% vs. 11.5%), exrtamedullary disease (59% vs. 46.2%) and penta-refractory status (43.6% vs. 34.6%). The median number of prior lines of therapy was 6 in both cohorts. Thirteen patients (33.3%) in the SCB and 11 (21.2%) in the nSCB received high intensity infusional chemotherapy (DCEP/PACE/HyperCVAD). Pre-CAR-T cytopenias tended to be less frequent in the SCB vs. nSCB cohort: ANC <1000 in 5.1% vs. 13.5%, Hgb <8 in 23.1% vs. 21.2%, and platelets <50K in 28.2% vs. 40.4%. Median plasmacytosis in the bone marrow prior to CAR-T in the SCB group was 35% and 47.5% in the nSCB group. In the SCB cohort, 2 patients harbored DNMT3A mutations, one of whom had CCUS. Ide-cel was administered in 64.8% and cilta-cel in 35.2% of all patients. The rates and grades of cytokine release syndrome did not differ between groups. Six patients (15.4%) had HLH in the SCB group vs. none in the control group. All (100%) SCB patients received growth factor support; 58% also received TPO agonists. In the nSCB group, 43 patients (82.7%) received growth factor, and 16 patients (30.8%) received TPO agonists. Out of 24 pre-SCB bone marrow biopsies available, only 1 patient had relapsed MM while the remainder had hypocellular marrows. Median CD34+ cell dose was 2.93 million/kg (range: 1.76-23.55) administered at a median of 53 days post-CAR-T (range 24-265). All but one patient (97.4%) in the SCB group achieved hematologic recovery; median time to recovery was 24 days (range 9-87). No new toxicities attributable to SCB were observed. On day 90 post CAR-T infusion, SCB patients had higher median ANC (2.12 vs. 1.59x109/L, p=0.277), Hgb (10.6 vs. 8.7g/dL, p=0.002), and platelet counts (135 vs. 35K/L (p<0.001). Minimal residual disease negativity was achieved in 82.4% (SCB) vs. 83.3% (nSCB). Infections occured in 53.8% and 48.1% of SCB and nSCB cohorts. All serious infections occurred prior to SCB. There were 12 deaths in the SCB group (7 from disease progression, 2 from infection, 1 from neurotoxicity (NT), and 1 unknown) and 27 in the nSCB group (22 from progression, 3 from infection, 1 from HLH, 1 from NT). After a median follow-up period of 12.6 months in the SCB cohort and 11.6 months in the nSCB arm, the mPFS was 11.0 months and 8.2 months, respectively. The mPFS was 10.6 months (SCB) and 5.8 months (nSCB) (p=0.216), and 11.0 months (SCB) and 10.9 months (nSCB), for ide-cel and cilta-cel treated-patients, respectively. Median OS was not reached vs.12.3 months in the SCB vs. nSCB groups, respectively. Conclusion: Overall, SCB was safe and effective in promoting rapid hematologic recovery in nearly all patients. Compared to controls, SCB recipeints had significantly higher Hgb and platelet levels by day 90 post-CAR-T infusion. SCB was associated wih a near doubling of PFS in patients who received ide-cel, though interpretation is limited by non-randomized design and small sample size. Further study is needed to optimize paient selection, timing, and integration of SCB into CAR-T care.

Abstract Introduction: While the incidence of multiple myeloma (MM) is 2-3 fold higher in Black compared to white individuals, the impact of racial differences on treatment outcomes remains unclear due to the confounding effect of socioeconomic barriers and disparities in access to effective therapies and clinical trials. In this study, we explored the relationship between race, social deprivation, and outcomes in newly diagnosed MM (NDMM) patients (pts) receiving modern therapies with triplet or quadruplet regimens. Methods: Pts with NDMM diagnosis, who received first line treatment between 2015-2025, and had data available on response and survival outcomes were identified through the ASH Research Collaborative MM Data Hub (a real-world database with pts across 11 U.S. institutions). Data on patient demographics (age, race, ethnicity, sex), disease risk status (ISS/R-ISS stage, FISH cytogenetics), treatment regimens (triplet vs quadruplet, anti CD38 monoclonal antibody-based vs not), and disparity measures were abstracted from electronic medical records. Race and ethnicity were self-reported by pts. Social Deprivation Index (SDI) score was calculated based on ZIP code, where higher scores reflect greater deprivation. Progression free survival (PFS) was defined as time from start of treatment until progression or death. Overall survival (OS) was defined as time from start of treatment until death from any cause. Kaplan-Meier methods were used to compare PFS and OS between groups, and cox regression models with log-rank tests were used to evaluate the influence of various factors on outcomes. Results: A total of 1,743 patients were identified; 1,116 (63.8%) identified as non-Hispanic White (NHW) and 402 (23.3%) as non-Hispanic Black (NHB) [note: 85 pts (4.9%) were Hispanic but not included due to limited numbers]. The median age (years) at the start of treatment (61.8 vs. 65.6) was lower for NHB compared to NHW pts (p<0.001). The proportion of females was greater in NHBthan NHW pts(53.5% vs. 41.1%, p=0.0016). Median SDI scores were significantly higher for NHBcompared to NHW pts (68.4 vs. 39.4; respectively; p<0.001), reflecting significantly higher rates of social deprivation. While NHB ptshad higher rates of advanced stage disease (ISS III 26.9% vs. 20.9%, p=0.009), lower rates of autologous stem cell transplant (ASCT) (56.7% vs. 63.6%, p=0.014), and longer median time from treatment initiation to ASCT (6.5 vs. 5.9 months, p=0.043), the rates of standard risk cytogenetics on FISH (72.3% vs. 77.6%), and utilization of CD38 monoclonal antibody-based regimen (29.9% vs. 27.7%) were similar between the two groups. Best response after treatment initiation was similar between the NHB and NHW pts (p=0.12) with complete response 45.7% vs. 52.6% and very good partial response 37.3% vs 34.7%; respectively. However, time to best response (months) was longer in NHB pts (7.2 vs. 6.5, p=0.005). Median follow-up for OS was 4.2 years (95% CI 3.9-4.4; 182 OS events) and for PFS was 1.3 years (95% CI: 1.1-1.6; 302 PFS events) across the two groups. Unadjusted PFS was similar for NHB vs NHW pts (HR=1.05, 95% CI: 0.81- 1.36; median: 5.0 vs 4.9 years; 3-year PFS: 66% vs. 71%). Similarly, unadjusted OS was not significantly different in NHB vs NHW pts (HR=1.12, 95% CI: 0.79-1.59; 5-year OS: 86.4% vs 85.6%). Higher SDI scores were significantly associated with worse OS (HR=1.07, 95% CI: 1.02-1.12; p=0.0065) but not PFS (HR=0.99, 95% CI: 0.95-1.02; p=0.46). Though not statistically significant, univariate analyses indicated a greater impact of high SDI scores (≥70, 75th percentile across all pts) in NHW (HR=1.45, p=0.068) than in NHB pts (HR=0.78, p=0.35) for OS. Adjusting for age, sex, ISS stage, and SDI, NHB did not appear to have worse OS (HR=0.75, 95% CI: 0.35-1.60; p=0.46) or PFS (HR=1.23, 95% CI: 0.78-1.96; p=0.37) compared to NHW pts. Conclusions: Our study represents a diverse population enriched for pts who received modern day standard of care frontline therapies including triplet and quadruplet regimens with or without ASCT. Based on SDI scores, higher social deprivation levels were seen in NHB compared to NHW pts without a difference in outcomes between the two races. Our analysis supports that higher social deprivation among different races rather than race and ethnicity alone may drive differential outcomes and adjustment for factors like SDI is critical to interpretation of survival outcomes by race.

Abstract Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL who were treated with the B-cell maturation antigen–directed chimeric antigen receptor T-cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients; 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression-free survival (mPFS) was 9.0 months (95% confidence interval [CI], 4-15) and the median overall survival (mOS) was 13.0 months (95% CI, 8 to not estimable [NE]). The 1-year cumulative incidence of progression or death was 72%, and the 1-year cumulative incidence of death was 47%. Patients who received cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (>23 months [NE] vs 9.0 months) when compared with those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI, 17.4-68.5) with cilta-cel, whereas all patients treated with ide-cel progressed or died within 12 months of infusion. The rates of hematologic and nonhematologic toxicities were similar between patients treated with cilta-cel and those treated with ide-cel and were consistent with those reported in patients with MM. In this first multicenter study that evaluated patients with PCL who were treated with standard-of-care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes when compared with historic standards.

Abstract Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), 2 B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T-cell (CAR-T) therapies, have transformed outcomes for relapsed/refractory multiple myeloma; however, the 6 to 8 weeks manufacturing time risks disease progression or death in up to 10% of patients. Talquetamab, a G-protein–coupled receptor, family C, group 5, member D (GPRC5D)–targeting bispecific antibody, represents a promising option. We performed a multi-institutional retrospective analysis across 20 centers (18 United States, 2 Germany) evaluating talquetamab as a bridging therapy prior to cilta-cel or ide-cel. Among 134 patients receiving talquetamab, 119 proceeded to CAR-T (n = 98 cilta-cel, n = 21 ide-cel). Reasons for not proceeding (n = 15) included progression (n = 7), manufacturing failure (n = 6), or patient decision (n = 2). Median age was 65 years and had median 5 prior lines of therapy. Notably, 85% would not have met CARTITUDE-1/KarMMa eligibility criteria. Talquetamab was administered for a median 23 days. Toxicity was manageable: no grade ≥3 cytokine release syndrome (CRS), 2% grade 3 immune effector cell–associated neurotoxicity syndrome (ICANS) and grade 1 to 2 talquetamab unique toxicities (70% oral, 38% skin, and 17% nail; 60% resolved). Talquetamab achieved 71% response rate. After CAR-T, 88% responded (54% complete response), with low-grade toxicities (2 grade ≥3 CRS, 1 grade 3 ICANS, and 5% grade ≥3 infections). Two cases of facial palsy and 1 acute myeloid leukemia occurred. Talquetamab correlated with sustained soluble BCMA decline and peak CAR-T expansion around day 14. Talquetamab bridging appears safe, enabling the majority of difficult-to-treat patients to successfully proceed to BCMA CAR-T therapy.

Abstract Teclistamab is an anti-CD3-/B-cell maturation antigen (BCMA) bispecific antibody approved for use in relapsed/refractory multiple myeloma. We undertook a retrospective study of post-approval, real-world outcomes with teclistamab in the US Multiple Myeloma Immunotherapy Consortium. Among 509 patients, 89% would have been ineligible for the MajesTEC-1 trial, primarily due to prior BCMA-directed therapy, cytopenias, or diminished performance status. Cytokine release syndrome occurred in 54% (1.4% grade ≥3) and immune effector cell–associated neurotoxicity syndrome in 11% (2.2% grade ≥3), with no fatal events. Infections occurred in 42% and contributed to death in 5%. Partial response (PR) or better was achieved in 53% and very good PR or better in 45%. With 10.1 months of median follow-up, the estimated median progression-free survival (PFS) was 5.8 months and 12-month overall survival was 61%. Independent predictors of less than very good PR and shorter PFS included BCMA-directed chimeric antigen receptor T-cell therapy in the previous 9 months, high disease burden, lymphopenia, and elevated ferritin. Significance: T cell–engaging bispecific antibodies such as teclistamab represent an important new treatment modality for multiple myeloma and other blood cancers. This study evaluates the real-world safety and efficacy of teclistamab, including its activity in populations not represented in the initial phase I/II study, and identifies clinical variables associated with treatment response. See related commentary by Zweegman et al., p. 542