Prior BCMA-Directed Therapy Linked to Diminished Teclistamab Efficacy in Relapsed/Refractory Multiple Myeloma

Outcomes in patients with relapsed/refractory multiple myeloma (RRMM) treated with teclistamab (Tecvayli) appear to be influenced by prior exposure to BCMA-directed therapy (BCMA-DT). Findings from a retrospective study suggest a trend toward worse progression-free survival (PFS) and a lower likelihood of achieving an overall response (ORR) in this population, although these differences did not reach statistical significance in all analyses.¹

Investigators followed patients for a median of 9.9 months. They reported that patients with prior BCMA-DT experienced a PFS of 4.6 months (95% CI, 2.7–7.5), compared with 8.2 months (95% CI, 5.7–12.2) for patients without prior BCMA-DT (P =.017). The ORR was 48.7% in the prior BCMA-DT group vs 61.5% in those without prior BCMA-DT (P =.012). Similarly, the rate of very good partial response or better was reduced in the prior BCMA-DT cohort at 39.4%, compared with 52.6% in the cohort without prior BCMA-DT (P =.009). However, rates of achieving a complete remission were comparable between the 2 groups (22.3% vs 24.0%; P =.78).

In the prior BCMA-DT group, the 6-month overall survival (OS) rate was 69.3% (95% CI, 65.1%–78.2%) vs 71.3% (95% CI, 65.1%–78.2%) in group without prior BCMA-DT. The 1-year OS rate was 58.9% (95% CI, 51.6%–67.2%) in the prior BCMA-DT group vs 65.1% (95% CI, 58.1%–73.1%) in the group without prior BCMA-DT (P =.16).

Multivariable analysis indicated a trend toward lower ORR in those with prior BCMA-DT exposure, however, this was not statistically significant (HR, 0.64; 95% CI, 0.41–1.01, P =.057). Further, there was a trend suggesting worse PFS with prior BCMA-DT exposure, although this was not independently associated with PFS (HR, 1.23; 95% CI, 0.94–1.61; P =.13).

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. Data were collected from 13 US academic medical centers that were participating in the US Multiple Myeloma Immunotherapy Consortium.

The study included 385 patients overall, with 193 (50%) having received prior BCMA-DT. Across the entire cohort, the median age was 68 years (range, 61–74), 47% were female, and 37% were penta-class refractory. In addition, 26% had an ECOG performance status of 2 or more, 55% had high-risk fluorescence in situ hybridization (FISH) findings, and 26% had active extramedullary disease prior to teclistamab initiation.

In patients who received prior BCMA-DT, the median age was 67 years (range, 60–71), 35% were 70 years or older, 42.0% were penta-class refractory, 24.0% were ECOG performance status 2 or more, and 61.0% had high-risk FISH.

A breakdown of prior anti-BCMA agents revealed that 149 (77%) patients received 1 agent, 42 (22%) received 2 agents, and 2 (1%) had received 3 agents. Specifically, 47 (24%) patients had received an antibody-drug conjugate (ADC) only, 99 (51%) patients had received prior chimeric antigen receptor T-cell therapy (CAR T) only, 36 (19%) patients had received both ADC and CAR T, 6 (3%) patients had received a prior anti-BCMA bispecific antibody alone, and 5 (3%) patients had received other combinations.

Regarding safety, the overall incidence of any grade cytokine release syndrome (CRS) in the prior BCMA-DT cohort was 56%. Only 2 patients (1%) in this group experienced grade 3 CRS, and no patients experienced a grade 4 or greater CRS event. For this cohort, the median time to CRS onset and to maximum CRS grade was 3 days. The overall incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 12% in the prior BCMA-DT cohort, with 3% of patients having grade 3 ICANS and no patients experiencing a grade 4 or greater ICANS event.

Danai Dima, and colleagues underscored the significance of these findings noting that “this is the largest study evaluating the outcomes of teclistamab in patients with RRMM and prior BCMA-DT exposure, a population that was initially excluded from the landmark MajesTEC-1 trial (NCT04557098).” They concluded that the findings support the use of teclistamab as a viable treatment option in patients with prior BCMA-DT exposure, especially if the prior BCMA-DT was not a bispecific antibody.

REFERENCE:

Dima D, Vazquez-Martinez MA, Davis JA, et al. Outcomes of teclistamab in patients with relapsed/refractory multiple myeloma with prior exposure to BCMA-directed therapy: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium. Blood Cancer J. 2025;15(1):111. Published 2025 Jun 25. doi:10.1038/s41408-025-01314-9