(PA-094) Early Mortality Associated with Real-World Bispecific Antibody Therapy for Relapsed/Refractory Multiple Myeloma

Teclistamab (Tec) is the first approved BCMAxCD3 bispecific antibody (bsAb) for patients (pts) with relapsed/refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. After a median follow-up of 14.1 months, 68 deaths (41.2%) were reported including 41 (24.8%) from progressive disease (PD) and 20 from infections (13 from COVID-19). Herein, we present an analysis of early mortality defined as death within 12 months of starting a bsAb for RRMM.

Methods:

This is an international multicenter retrospective study of pts with RRMM treated with bsAb on-label at 9 academic centers from 5 countries (US, UK, Greece, Spain, and Canada). Pts with RRMM treated with tec at the respective institutions between 5/24/22 to 1/4/24 were included in this analysis. Median follow-up was 14 months with data collected until 11/29/24. High-risk cytogenetic abnormality (HRCA) was defined as 1q+, t(4;14), t(14;16), t(14;20), and/or del(17p). Response was assessed using the IMWG criteria for response. Patient characteristics were summarized by frequency (percentage) or median (interquartile range [IQR] or range). Cox regressions were used to evaluate covariate effects on early mortality.

Results:

The 223 pts included in this analysis had the following characteristics: median age of 67 (range 33-91) with 24% ≥75 years; 45% female; 49% (86/176) with HRCAs; 29.4% (37/126) with extramedullary disease (EMD). Pts received a median of 6 (IQR, 4-8) prior lines of therapy with 52% (107/206) being penta-drug refractory and 94 (42%) pts with prior BCMA-directed therapy (DT; 29.8% antibody-drug conjugate [ADC] alone; 45.7% CART alone; 6.3% bsAb alone; 17.0% ADC and CART). ORR for 206 response-evaluable pts was 66% (25.2% ≥CR, 33.5% VGPR, 7.3% PR).

Among the 223 pts, 80 (36%) died within 12 months of tec initiation including 61 who died ≤6 months. In this subgroup, median age was 66 (36-91), 58% were penta-refractory, 49% had prior BCMA-DT, 46% (19/41) had EMD, and 55% (35/63) had HRCAs. ORR for 70 response-evaluable pts was 31% (3 ≥CR and 10 VGPR); 31 pts had PD. Cause of death included 52 (65%) due to PD, 12 (15%) from infection, 2 from PD and infection, 10 (12.5%) due to other causes (notably, 3 from failure to thrive, 1 treatment-related, 1 cardiopulmonary failure, 1 intracranial hemorrhage, 1 liver failure, 1 sudden death), and 4 unknown. Regardless of the cause of death, 80% (63/79) of pts with early mortality had evidence of PD at the time of death. On multivariate analysis, early mortality was associated with lack of response to tec (HR 2.15, 95%CI, 1.11-4.18; P=0.02) and presence of HRCA (HR 1.73, 95%CI, 1.03-2.88, P=0.04).

Conclusions:

In this international real-world analysis of early mortality associated with bsAb therapy, the most common cause of death was progressive disease followed by infection. Risk factors for early mortality include lack of response and the presence of HRCAs. Additional data including pts treated with other bsAbs (talquetamab, elranatamab) will be presented at the meeting.