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Background: Tec is a BCMA-directed bispecific antibody (BsAb) approved for RRMM after ≥4 prior lines of therapy (LOT) based on the MajesTEC-1 trial. However, patients who had previously received a BCMA-DT were excluded from MajesTEC-1. Herein, we evaluated outcomes of RRMM patients with prior exposure to BCMA-DT treated with standard-of-care Tec. Methods: This was a multicenter retrospective cohort study. We compared variables between different groups using Chi-squared and Kruskal-Wallis tests, and assessed progression free survival (PFS) and overall survival (OS) using Kaplan Meier and Cox proportional hazards model. We used the maximally selected rank statistics method to determine the optimal cut-off point for continuous variables to find the most significant difference in PFS among different groups. Results: A total of 385 patients were included in this study. 193 patients had received a prior BCMA-DT, of whom 77%, 22%, and 1% had received 1, 2, and 3 prior anti-BCMA agents, respectively. In patients who had received a prior BCMA-DT, 35% were aged ≥70 years, 24% had ECOG performance status (PS) ≥2, 61% had high-risk FISH, 32% had extramedullary disease (EMD) at Tec initiation, and 42% were penta-refractory. Compared to the cohort without prior BCMA-DT (n=192), patients who were treated with prior BCMA-DT were more likely to have high risk FISH (61% vs 49%, p=0.02), and higher median number of prior LOT (7 vs 5, p <0.001). The specific types of prior BCMA-DTs with the respective overall response rate (ORR) to the most recent prior BCMA-DT were: antibody drug conjugate only (ADC, n=47, ORR 43%), chimeric antigen receptor T-cell therapy only (CAR T, n=99, ORR 86%), BsAb only (n=6, ORR 100%), ADC + CAR T (n=36, ORR 56%), and other ADC/CAR T/BsAb combinations (n=5, ORR 60%). Median follow up was 9.9 (95% CI:9.5-10.6) months. Patients with prior receipt of BCMA-DT had a lower ORR (51.4% vs 61.5%; p=0.012) and ≥very good partial response rate (39.4% vs 52.6%, p=0.009), but similar ≥complete response rate (22.3% vs 24%; p=0.78) to Tec compared to those without prior BCMA-DT. Moreover, patients with prior BCMA-DT had worse median PFS compared to patients without prior BCMA-DT (prior BCMA-DT: 4.6 months, 95% CI: 2.7-7.5; without prior BCMA-DT: 8.2 months, 95% CI: 5.7-12.2; p=0.017). On multivariable analysis incorporating prior BCMA-DT, age, cytogenetics, EMD, and ECOG PS, receipt of prior BCMA-DT was not independently associated with PFS (HR 1.25, 95% CI 0.95-1.64, p=0.1). The estimated 1-year OS rate was 58.9% (95% CI: 51.64-67.2) for the prior BCMA-DT group vs 65.1% (95% CI: 58.1-73.1) for the group without prior BCMA-DT, p=0.16. For the prior BCMA-DT cohort, response rates to Tec were numerically higher in patients who received CAR T (ORR 51.2%) followed by ADC (ORR 45.5%), and bispecific (ORR 30%) as their most recent prior BCMA-DT (p=0.39). No significant difference in PFS was 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. Patients who responded to Tec had a numerically longer median time from most recent BCMA-DT exposure to Tec initiation compared to non-responders: 10.5 vs 7.5 months, p=0.48. We found that the optimal cut-off for time from last BCMA-DT exposure to Tec initiation was 8.7 months. Patients with > 8.7 months between last exposure to prior BCMA-DT and Tec initiation had a superior median PFS with Tec (8.1 months, 95% CI: 4.6-11.7) compared to patients with < 8.7 months from last exposure to prior BCMA-DT (2.5 months, 95% CI: 1.1-5.7), p=0.001. The toxicity profile for patients with prior BCMA-DT was similar to those who had not received a prior BCMA-DT. Grade ≥2 CRS occurred in 8.7% vs 13% (p=0.18), and grade ≥2 ICANS in 7.7% vs 6.7%, (p=0.85) of patients with and without prior BCMA-DT, respectively. Patients in the prior BCMA-DT cohort were more likely to have grade 3 thrombocytopenia in the first 30 days after Tec initiation (10.7% vs 6.6%; p=0.08). Conclusion: This is the largest study to date of any BCMA-directed BsAb among BCMA-exposed patients. Receipt of prior BCMA-DT was associated with a trend toward worse PFS, although not statistically significant, and lower likelihood of attaining an overall response. Waiting >9 months between sequencing BCMA therapies may be associated with improved PFS. D.D., M.A.V.M., J.A.D: co first authors; F.A., C.F., L.S.: co senior authors

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.

The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients.

Introduction: Lymphodepletion (LD) chemotherapy is critical for the efficacy of CAR-T therapy by eradicating immunosuppressive cells, inducing costimulatory molecules, and promoting expansion and persistence of CAR-T cells. It also can contribute to an increased risk of infections, cytopenia, and other toxicities. We evaluated the utilization of varying LD regimens used in standard-of-care (SOC) autologous B-cell maturation antigen-directed (BCMA) CAR-T therapy with ide-cel or cilta-cel for relapsed/refractory multiple myeloma (RRMM) and the effect on outcomes and toxicity. Methods: Data were retrospectively collected from patients with RRMM who underwent LD and CAR-T cell infusion by December 31, 2022, from 13 US academic institutions with SOC ide-cel or cilta-cel. Response rates and other categorical variables, specifically LD regimen, were tested for association using Wilcoxon rank-sum (or Kruskal-Wallis for three or more groups) or Fisher's exact tests, respectively. Results: A total of 523 patients were infused at the time of data cut-off with 489 patients evaluable for safety and survival analyses; 368 (75%) were infused with ide-cel and 121 (25%) with cilta-cel. The median age was 65 years old (range 30-90) with 206 females (42%) and 283 males (58%), and 13% with ECOG performance status ≥ 2 at time of LD. Fludarabine and cyclophosphamide (Flu/Cy) LD was used in 422 patients while 67 patients received other LD regimens including bendamustine-based (n = 35, 52%), cladribine-based (n = 25, 37%) or cyclophosphamide alone (n = 7, 10%). The primary reason for use of Flu/Cy LD was institutional guidance or SOC in 378 patients (90%), while the primary reason for use of other LD regimens was due to the fludarabine shortage in 65 patients (97%) with 3% citing physician's choice or institutional guidance. No significant difference was identified among response outcomes, with those receiving Flu/Cy LD achieving an ORR of 84% compared to 81% with other LD regimens (p = 0.59) and no difference observed in rates of ≥ VGPR (66% Flu/Cy LD vs 60% other LD; p = 0.48). Of those evaluable for MRD at 1 and 3 months, the MRD negative rate at 10 -6 for those with Flu/Cy LD was 77% (n= 137) and 77% (n=113) and with other LD regimens was 66% (n=35) and 79% (n=28), respectively. At a median follow-up of 9.7 months, no statistically significant difference was noted in median progression free survival (mPFS) with Flu/Cy vs other LD regimens (9.3 mos vs NR) or overall survival (OS) (19.4 mos vs NR). When stratified by type of CAR-T therapy, treatment with bendamustine-based LD was associated with an inferior mPFS compared to those receiving Flu/Cy LD in patients treated with ide-cel (3.8 vs 8.5 mos; p=0.0056), though not by multivariate analysis. Univariate analysis of patients treated with ide-cel between Flu/Cy and bendamustine LD did not reveal any significant differences in age, gender, ECOG, R-ISS stage, extramedullary disease, high-risk cytogenetics or renal dysfunction (Cr < 45 ml/min). LD regimen was not a predictor for PFS on multivariable analyses amongst patients treated with ide-cel, while ECOG ≥ 3 (hazard ratio [HR]= 4.44, 95% confidence interval [CI]= 1.40, 14.08) and t(4,14) (HR= 2.02, 95% CI=1.14, 3.59) were associated with worse PFS. No difference in mPFS by LD regimen was observed in patients receiving cilta-cel, which was a smaller cohort (mPFS: Flu/Cy 11.7 mos, bendamustine-based NR, cladribine-based NR, cyclophosphamide NR). Rates of all grade CRS (81% vs 70%), Grade ≥ 3 CRS (3% vs 3%), all grade ICANS (19% vs 12%, and Grade ≥ 3 ICANS (4% vs 2%) were similar among those receiving Flu/Cy or other LD regimens, respectively. Patients receiving Flu/Cy LD were less likely to have any grade cytopenia at 1 month (33% vs 55%, p < 0.001) and 3 months (52% vs 69%, p < 0.001), with no observed difference in infection rate. Conclusions: The fludarabine shortage experienced in the US in late 2022 necessitated the use of alternative LD regimens with BCMA-directed CAR-T therapy with most centers relying on bendamustine- or cladribine-based regimens. Use of bendamustine-based LD was associated with inferior PFS in patients receiving ide-cel on univariate analysis, but not on multivariate analysis after adjusting for other prognostic factors. In summary, there is no clear difference in efficacy or safety between Flu/Cy and non-Flu/Cy LD in patients receiving BCMA-directed CAR-T therapy. *Authors contributed equally

Background: Daratumumab-based combination with proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs) have revolutionized the treatment outcomes of relapsed/refractory multiple myeloma (RRMM). Several daratumumab-based triplet combinations have been approved for the management of RRMM, but outcomes of daratumumab-based triplets in patients with high-risk cytogenetics RRMM (HC-RRMM) are not well described in the literature. This study aimed to evaluate the clinical outcome of daratumumab-based regimens in patients with HC-RRMM who are daratumumab-naïve. Methods: A retrospective review of 110 patients with HC-RRMM who received daratumumab-containing regimens from 6/2016 through 2/2023 at the University of Kansas Medical Center, in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC) was conducted. Daratumumab was combined with bortezomib/dexamethasone (DVd), carfilzomib/dexamethasone (DKd), and pomalidomide/dexamethasone (DPd) for treatment of RRMM. HC-RRMM was defined as patients with one or more cytogenetic abnormalities (on FISH panel) including -17/del(17p), t(4;14), t(14;16), t(14;20), or amplification of 1q. Responses to therapy including overall response rate (ORR), complete response or better (≥CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. Descriptive statistics were used to summarize patient and disease characteristics, along with efficacy outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier methods. Results: Of the 110 patients with HC-RRMM, the median age was 66 years (range 43-84), 83 (75%) were Caucasian, 60 (54%) had IgG isotype, 41 (37%) had revised international staging system (R-ISS) stage III disease, 35 (32%) had extramedullary disease (EMD), 57 (52%) patients had one high-risk cytogenetic (HC) abnormality, 49 (44%) had 2 HC abnormalities, while four (4%) had 3 HC abnormalities. The median number of previous lines of therapy was 2 (1-4). Eighty-eight patients (80%) were lenalidomide refractory, while 53 patients (48%) had double refractory disease to both a PI and IMiD treatment. A total of 19 (17%), 27 (25%), and 64 (58%) patients received DVd, DKd, and DPd, respectively. The overall response rate (ORR) for the entire patient population was 73%, 45% had VGPR or better, and 35% achieved ≥CR. Median follow-up was 28 months (12.07-53.57), the median OS was 28 months (95% CI 23.2 - 43.9) and PFS was 8.03 months (95% CI 5.8 - 12.2) for all treatment groups. The median PFS for 1 HC vs ³ 2 HC was 14.8 vs 4.57 months (HR 1.72, 95%CI 1.17-2.72 p = 0.006), respectively. Similarly, median OS for 1 HC vs ³ 2 HC was 43.93 vs 22.47 months (HR 1.87, 95%CI 1.15-3.05, p = 0.011), respectively. (Figure 1). On multivariate analysis, R-ISS stage III, -17/del(17p), and the presence of more than one HC abnormality were associated with poor OS. The most common cause for treatment discontinuation was progressive disease, accounting for 73% of patients in the whole cohort. As for each daratumumab-based triplet, discontinuation due progression occurred in 78%, 48%, and 83% in DVd, DKd, and DPd, respectively. Other causes of discontinuation included > grade 3 neuropathy, which occurred in 16% of patients receiving DVd, and cardiac events, which occurred in 11% of patients receiving DKd. Treatment-related mortality occurred in 2% of patients in the whole cohort. At the time of evaluation, 14 patients remain on treatment. Conclusion: Advanced stage R-ISS disease at diagnosis, presence of -17/del(17p), and 2 or more HC abnormalities were associated with poor prognosis reflected by worse PFS and OS in HC-RRMM treated with daratumumab-based therapies. A larger cohort or a prospective study in patients with HC-RRMM is needed to compare long-term outcomes between daratumumab-based therapies (DKd, DVd, and DPd).

Introduction: Novel B cell maturation antigen (BCMA) directed therapies including chimeric antigen receptor- T (CART) such as idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have been approved since 2021. More recently in 2022, the first BCMA-directed T-cell-engager (TCE), teclistamab (tec), was also approved for the treatment of relapsed/ refractory multiple myeloma (RRMM). Unfortunately, limited access to these therapies worldwide appears to be a major challenge. This study aims to gain insight into the variation in access to these therapies, and barriers to access. Methods: This study was an electronic survey of 176 hematologists/oncologists in centers across the globe outside the USA who treat MM and was conducted in collaboration with US Myeloma Innovations Research Collaborative (USMIRC). The survey was distributed from June 18 th 2023, to July 15 th 2023. Sections included demographics of respondents, availability of drugs in the country, and barriers to access. The respondents categorized each medication as “easily accessible”, “moderately accessible,” “not readily accessible” or “no access”. To categorize a country/region as having “adequate access”, the cut-off was 60% of responders affirming easy/moderately easy access. We investigated whether higher healthcare spending in a country is associated with better drug accessibility. Health expenditure (HE) of a country's Gross domestic product (GDP) from the World Bank was utilized to categorize countries into two groups: “High healthcare investing nations” (HHIN), which included countries spending >10% of their GDP on healthcare, while “Low healthcare investing nations” (LHIN) included countries spending <10% on healthcare. An interim analysis is reported. Results: There were 95 (54%) completed responses from 33 countries. Most (51%) were university-based academic centers and only 17% were centers with a dedicated focus in plasma cell disorders. Only 17% reported adequate access to ide-cel and 16% to cilta-cel, while a limited, yet higher number of respondents had adequate access to tec (23%). Refer to Table 1 Access to CART (ide-cel and cilta-cel): Globally, only 3 of the 33 (9%) countries had access to ide-cel, cilta-cel or both (France, Morocco, Saudi-Arabia). All other countries had limited access. When grouped by continent, none of the continents had adequate access to CART. Both HHIN and LHIN countries had limited access to CART. Access to TCE (tec): Seven of the 33 (21%) countries had adequate access to tec (Switzerland, Netherlands, France, Portugal, Czech Republic, Morrocco, Saudi Arabia). All other countries had limited access. When grouped by continent, although Europe had the most access, none of the continents had adequate access to TEC. Both HHIN and LHIN countries had limited access to TCE, although relatively, TEC was more accessible compared to CART. Figure 1 summarizes access to CART and TCE Barriers to access: Other than Europe, the most common barrier for ide-cel, cilta-cel and tec was cited as financial burden for patients. Financial burden for patients as a top barrier for each of the products by continent was as follows: Asia (83%), South America (64%), Africa (71%) Australia (100%), and North America (100%). In Europe, for CART, financial burden remained a top barrier (50%) along with local agency approval (50% for ide-cel, 44% for cilta-cel). In Europe, the most cited barrier for TCE was the financial burden for patients (44%), while (33%) of oncologists reported no barrier to TCE. Reimbursement for CART and TCE in Europe requires phase 3 randomized controlled trial data, which is just emerging since 2022 for CART and relatively increased access may be due to the presence of compassionate use programs. Conclusion : The survey is the first attempt to highlight the significantly limited global access to novel therapies (ide-cel, cilta-cel, and tec) for the treatment of RRMM. All continents including HHIN had limited access to CART and TCE. Noticeably, CART is less accessible than TCE, even though approved earlier. The main barrier to both CART and TCE is reported as financial burden for patients. USMIRC in collaboration with oncologists worldwide, global agencies, governments, regulatory agencies, policymakers and industry partners, is planning to further explore restrictions to access to CART and TCE and strategies to overcome these barriers.

Abstract 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.

8013 Background: Ide-cel is an FDA-approved treatment for RRMM patients (pts). However, there is limited data on how BT for disease control during its manufacturing process affects clinical outcomes. Methods: Eleven US academic centers contributed data to this analysis without involvement from the manufacturer. By 5/1/2022, 235 pts had undergone leukapheresis, with 214 infused with a median follow up of 9 months (mos). BT was given between leukapheresis and CAR-T infusion. Results: In this analysis, 79% of pts (n = 170) received BT, which included alkylator-based in 35.5%, steroid and/or IMiD/Ab combos (IMiD combos) in 14%, PI combinations (PI combos) in 12%, and selinexor in 10%. BT recipients had higher ECOG PS 2-4, R-ISS 2-3, ferritin, and CRP before lymphodepleting (LD) chemo, however, no difference among BT subgroups. No difference in prior lines of therapy or penta-refractory between BT and No BT (NBT) groups or BT subgroups. Median cycle of the BT was 1 (1-7), with overall response rate (ORR) of 12%, with no difference among BT subgroups. Incidence and severity of CRS and ICANs were comparable in BT and NBT. However, pts who received BT had a longer median hospital stay compared to NBT, particularly in the alkylator/selinexor subgroups. There were no significant difference in cytopenias at day 90 post CAR-T between the BT and NBT or BT subgroups. For the 73% (n = 157) evaluable for day 90 response, there was no difference in the complete or ORR between the BT and NBT groups (41% vs. 52%; p = .2 and 84% vs. 87.5%, p = .8, respectively). Median PFS was worse at 8.1 mos in BT vs 11.5 mos in NBT (p = .03). Among BT subgroups, PFS was the longest with IMiD combos with median PFS not reached (NR), comparable to NBT, and was significantly longer than all other BT subgroups (p = 0.01). The median OS was 13.8 mos with BT and NR in NBT (p = .002). In BT subgroup analysis, alkylators had a shorter OS, although, this was not significant (p = .06). There was no significant difference in PFS and OS in relationship to response to BT (p = .6 and p = .9, respectively). Conclusions: Pts without BT had longer PFS and OS post ide-cel, likely reflective of less aggressive disease. Those who received BT with steroid/IMiD and Ab combos had similar PFS as NBT. However, BT choice is complicated by disease severity and should be evaluated per patient circumstances. [Table: see text]

8012 Background: Cilta-cel was FDA approved in 2022 for the treatment of RRMM. We evaluated the outcomes of patients treated with intended SOC cilta-cel. Methods: 12 US academic medical centers contributed data to this retrospective study. As of 12/31/2022, 177 patients were leukapheresed and 139 received cilta-cel. Results: The table describes the study population compared to the CARTITUDE-1 trial. More patients in our study had extramedullary disease (EMD, 35%) and high-risk cytogenetics (41%). 55% of the patients would not have met eligibility criteria for CARTITUDE-1. Common reasons for ineligibility were cytopenias (19%), prior BCMA therapy (14%), organ dysfunction (12%), oligosecretory disease (13%), and plasma cell leukemia (8%). 83% of the patients received bridging chemotherapy (overall response rate, ORR: 28%). Lymphodepletion included fludarabine (Flu) + cyclophosphamide (Cy): 81%, bendamustine: 11%, Cy: 4%, and cladribine + Cy: 4%. Median CAR-T cells infused were 0.6 million/kg (range: 0.1-0.9), and 19% of patients were treated on an expanded access protocol (EAP). Median follow-up was 2.3 months (range: 0-8). Cytokine release syndrome (CRS) was seen in 81% (≥ grade 3: 7%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (≥ grade 3: 8%) of patients. Tocilizumab, steroids, and anakinra were used in 61%, 44%, and 10% of patients, respectively. Delayed neurotoxicity (NT) was seen in 9% (cranial nerve palsy: 8, Parkinsonism: 2, others: 3). Grade ≥ 3 cytopenias at day ≥ 30 were seen in 75% of patients. Infections were seen in 32% of patients. Day 30 (N=115) and best response rates (N=118) were: ≥ partial response (PR), 75/80%; ≥ very good PR, 44/62%; and ≥ complete response (CR), 26/40%, respectively. In the non-EAP FluCy population (N=88), best ORR/≥CR were 89/49%. 17 patients died by data cut-off, 4 due to disease progression and 13 (9%) due to non-relapse mortality (NRM) (grade 5 CRS: 3, infection: 6, CRS/infection: 1, grade 5 ICANS: 1, delayed NT: 2). Conclusions: Patients treated with intended SOC cilta-cel had a favorable ORR (80%) despite a larger proportion of patients having high-risk features relative to trial patients and limited follow-up. Response rates were higher in patients receiving conforming products with FluCy conditioning (89%). Delayed NT and NRM were seen in 9% of patients. Results will be updated with continued follow-up. D.K.H., K.K.P, M.J., Y.L. & S.S. contributed equally. [Table: see text]

Despite advances in treatment, outcomes remain poor for patients with penta-relapsed refractory multiple myeloma (RRMM). In this retrospective analysis, we evaluated the survival outcomes of penta-RRMM patients treated with (BCMA)- directed therapy (BDT). We identified 78 patients with penta-RRMM. Median age was 65 years, 29 (37%) had R-ISS stage III disease, 63 (81%) had high-risk cytogenetics, and 45 (58%) had extra-medullary disease. Median LOT prior to penta-refractory state was 5 (3–12). Amongst penta-RRMM, 43 (55%) were treated with BDT, 35 (45%) were not treated with BDT. Type of BDT received included belantamab mafadotin 15 (35%), Chimeric Antigen Receptor T-cell therapy 9 (21%), BCMA monoclonal antibody 6 (14%), and Bispecific T-cell engager 2 (5%). Eleven (25%) patients received more than one BDT. No significant differences were identified between baseline characteristics for the two groups. Patients treated with a BDT had better median overall survival, 17 vs. 6 months, HR 0.3 p-value < 0.001. Poor performance status, white race, and high-risk cytogenetics were associated with worse outcomes, whereas using a BDT was associated with better outcomes. Patients with penta-refractory MM have poor outcomes. Our retrospective analysis showed a significant survival benefit using BDT when compared to non-BDT for patients with penta-RRMM.