How long is long enough? Outcomes with finite-duration bispecific antibody therapy in multiple myeloma.

Abstract

7538 Background: Bispecific antibodies (BsAbs) have shown unprecedented efficacy in relapsed/refractory multiple myeloma (RRMM), and finite-duration therapy is an increasingly common yet poorly studied strategy. We aimed to analyze outcomes in MM patients (pts) treated with finite-duration teclistamab (tec) or talquetamab (tal). Methods: This single-institution retrospective cohort study included pts treated with tec or tal monotherapy at UCSF from 7/2021 to 1/2025 for RRMM, excluding pts with prior BsAb exposure and pts receiving BsAbs as a bridge to CAR-T. Patient-, disease-, and treatment-related characteristics were collected and summarized descriptively. To assess the impact of treatment duration while mitigating immortal time bias, we conducted 6- and 9-month landmark analyses of PFS, comparing pts who discontinued treatment before the landmark with pts still on treatment. Patients with PD or death before the landmark were excluded. Multivariate analyses (MVA) of survival outcomes used Cox regression with the following covariates: age, IMS-IMWG risk, ISS stage, extramedullary disease (EMD), ECOG score, and prior BCMA exposure. Results: In total, 120 consecutive pts were included with median follow-up 13.7 mos. Forty stopped therapy early for reasons other than PD (finite) and 80 did not (non-finite). Among finite pts, median treatment duration was 4.7 mos (range 0.2-32.4), 24 stopped due to toxicity, and 16 due to sustained remission. Clinical characteristics including age, ISS, IMS-IMWG risk, and ECOG were balanced between groups, but finite pts had less EMD (7.5% vs 25.0%, p=0.03) and triple-class refractory status (52.5% vs 73.8%, p=0.03) than non-finite pts. ORR was 97.5% (60% CR+) and 73.4% (29.1% CR+) in finite and non-finite pts, respectively. For finite, non-finite, and all pts, respectively, median PFS was not reached (NR) with 24-mo PFS 63%, 7.9 mos, and 16.53 mos, while median OS was NR, 24.8 mos, and NR. For landmark analysis of patients alive and progression-free at 6 mos, 22 were off therapy and 55 pts remained on therapy at 6 mos and median PFS was NR and 29.5 mos, respectively (univariate regression HR 0.71 [0.32-1.57], p=0.4). On MVA, the hazard ratio also favored the on-therapy group (HR 0.51 [0.21-1.22], p=0.13). At the 9-month landmark, 20 pts were off therapy and 42 pts were on, with univariate regression HR 1.71 (0.58-5.11, p=0.3) and MVA HR 1.1 (0.32-3.76, p=0.87). Conclusions: Finite-duration BsAb therapy was associated with durable responses in selected patients, although this group had more favorable baseline disease characteristics. In adjusted landmark analyses, early discontinuation before 6 months was associated with numerically shorter PFS without statistical significance, while PFS was comparable at the 9-month landmark. Randomized-controlled trials are required to define optimal treatment duration.