Cellular and T cell engager Immunotherapy

(OA-02) Sustained Remission After Limited-Duration of Bispecific Antibody Therapy in Patients with Relapsed/Refractory Multiple Myeloma

Wednesday, September 17, 2025

11:30 - 11:40 East Coast USA Time

Location: Room 701

Abstract Presenter(s)

Meera Mohan, MD

Assistant Professor
Medical College of Wisconsin
Milwaukee, Wisconsin

Introduction: While bispecific/multispecific antibodies (BsAbs) have transformed the treatment of relapsed/refractory myeloma (RRMM), their continuous administration until progression can result in T-cell exhaustion and elevated infection risk. Hence, data on fixed-duration strategies are urgently needed.

Methods: We conducted a multi-national retrospective cohort study of patients who received BsAbs either through early-phase clinical trials or as standard-of-care, subsequently discontinued treatment for reasons other than disease progression or death and were alive in remission for at least 3 months post-discontinuation.

Results: Of 720 consecutive patients screened, 78 were included, with 72% receiving BCMA-targeted BsAbs, 19% GPRC5D-targeted BsAbs, and 9% multi-specific antibody (BCMA + GPRC5D). The median age was 70 (range 26-86) years, 55% were female, 18% identified as Black, 47% had ≥1 high-risk cytogenetic abnormality, and 8% had extramedullary disease (EMD). The median BsAb treatment duration prior to discontinuation was 7 months (range, 1-40), with 80% in complete response (CR) at discontinuation. The most common reason for treatment discontinuation was infections (n=34; 44%), followed by ectodermal toxicities (n=12; 15%). At a median follow-up of 16 months from treatment discontinuation, the relapse-free survival (RFS) at 2 years was 67% (95% CI, 55%, 80%). Notably, the 2-year RFS in patients with ≥6 prior lines of therapy was 48%, compared to 79% and 78% respectively in those with 1-3 and 4-5 prior lines. On multivariable analysis for RFS, factors independently associated with inferior RFS included presence of EMD (HR [hazard ratio] = 7.88; 95% CI 1.95, 31.8; p = 0.004), number of prior lines of therapy (HR = 1.79; 95% CI 1.32, 2.43; p = < 0.001), and partial remission (PR) at the time of treatment discontinuation (HR = 28.3; 95% CI 2.06, 3.9; p = 0.012). The cumulative incidence of grade 3 or higher infections post-discontinuation was 22% at 1 year, 32% at 2 years, and 38% at 3 years, with a decrease in cause-specific hazard of first grade ≥3 infection as patients moved further away from treatment. Notably, among the two patients who resumed the same BsAb (both BCMA-targeting) at disease progression, one achieved CR and one did not respond.

Conclusions:

In summary, our data demonstrates that a substantial proportion of patients can sustain disease remission after discontinuation of BsAbs in relapsed/refractory myeloma, with 2-year RFS in patients with up to 5 prior lines of therapy approaching ~80%. In patients achieving deep response with BsAbs, randomized controlled trials (RCTs) are needed to answer whether a limited-duration approach is non-inferior in terms of efficacy to treatment-until-progression, and potentially safer in terms of cumulative infection risk over time.