Bi-specific T-cell engagers as a bridge to ciltacabtagene autoleucel in Relapsed/Refractory multiple myeloma: Real-world outcomes in an underserved urban population Free

Introduction Patients with relapsed/refractory multiple myeloma (RRMM) face limited treatment options and poor outcomes, with median overall survival of around one year. Responses diminish with successive lines of therapy due to resistance mechanisms, clonal evolution, and immune evasion, underscoring the need for novel therapeutic options. Ciltacabtagene autoleucel (cilta-cel), a B-cell mature antigen (BCMA)-directed autologous CAR-T cell therapy, and Bi-specific T-cell engagers (BiTEs) such as talquetamab (GPRC5D-targeted) and teclistamab (BCMA-targeted), have demonstrated durable responses in heavily pretreated multiple myeloma populations. However, data on their combined and sequential use remains limited. This knowledge gap is even wider among racially diverse, underserved cohorts who face barriers to accessing these treatments. Here, we report real-world safety and efficacy data on cilta-cel and BiTE bridging in a predominantly underserved population treated at a large urban academic center in New York City.

Methods We conducted a single-center, retrospective chart review of adult patients with relapsed/refractory multiple myeloma who underwent leukapheresis and received ciltacabtagene autoleucel (cilta-cel) at Montefiore Medical Center. A subgroup analysis was performed for patients who had received bispecific T-cell engagers prior to cilta-cel infusion. In all cases, leukapheresis for harvesting of cells for CAR-T therapy was done prior to initiation of BiTE therapy. Data was collected manually from the electronic health record, patient demographics, prior treatment regimens, cytogenetic data such as del(17p), t(4;14) and other high-risk features as defined by the International Myeloma Working Group (IMWG). Our primary endpoint was safety, with a focus on adverse events observed with cilta-cel alone compared to those after BiTE bridging. Secondary endpoints included overall response rate (ORR) and evidence of disease progression. Comparisons between groups were assessed using a two-sided Fisher's exact test.

Results From September 2023 to March 2025, 49 patients with RRMM received cilta-cel, with follow-up collected through June 2025. Median age at infusion was 65 years. Median time from leukapheresis to CAR-T infusion was similar between patients receiving BiTE bridging (63 days) and those without (64 days). Our cohort included 38.9% (n=19) patients identifying as non-Hispanic Black and 44.9% (n=22) as Hispanic. High-risk MM was identified in 20% of cases, including 4.1% (n=2) with CNS involvement and 14.3% (n=7) with extramedullary disease. Most patients were triple-class (36.7%) or penta-class refractory (57.1%). 17 patients received BiTE therapy prior to cilta-cel infusion (talquetmab n=12, teclistamab n=3, others n=2).

CRS occurred in 59% of patients who received a BiTE bridge versus 81% without bridging (p=0.17). ICANS was not observed in the BiTE group but occurred in 4 non-bridged patients (p = 0.29). Prolonged cytopenias >30 days were comparable (52.9% vs 50%, p=1.0). BiTE-related toxicities included dysgeusia alone (35%) and dysgeusia with palmar desquamation (11.8%), while 35% did not have any reported toxicities. Overall response rate (ORR) post-cilta-cl was 91.9% among both groups (63.3% CR, 20.4% VGPR, 8.2% PR), with similar CR rates between BiTE and non-BiTE-bridged groups (64.6% vs 62.2%, p=0.52). 3 deaths occurred during follow-up (2 BiTE, 1 non-bridged). At last follow-up, 88.2% of BiTE-bridged patients and 84.4% of non-bridged patients remain progression-free.

Conclusions In our racially diverse, real-world cohort of RRMM patients, cilta-cel shows promising efficacy (ORR 91.9%) and favorable safety profile, consistent with outcomes from prior trials in predominantly European populations. To our knowledge, this is the first study assessing the use of BiTEs as a bridge to cilta-cel in a majority Black and Hispanic population. BiTE bridging was feasible, did not delay CAR-T infusion, and showed comparable safety to non-bridged patients, with manageable BiTE-related toxicities. Post-cilta-cel outcomes were similar regardless of bridging, supporting BiTEs as a safe and effective strategy to maintain disease control prior to cilta-cel without compromising CAR-T efficacy. Our findings underscore the critical need to improve access to therapies in racially and ethnically diverse populations, who remain disproportionately affected by multiple myeloma and underrepresented in clinical research.