Long-lasting remission after limited-duration bispecific antibody in relapsed/refractory MM
Overview
A retrospective study of 23 patients with relapsed/refractory multiple myeloma (MM) who discontinued bispecific antibody (bsAb) therapy for reasons other than progression showed that over 80% remained progression-free at 1 year. Fixed-duration bsAb treatment may provide durable remissions while potentially reducing toxicity and treatment burden.
Background
Bispecific antibodies targeting BCMA and GPRC5D have shown high response rates (57–71%) in relapsed/refractory MM, with teclistamab, elranatamab, and talquetamab receiving FDA accelerated approval. Traditionally, bsAb therapy is given continuously until progression or intolerance, but continuous dosing can cause T-cell exhaustion, increased infection risk, and potential relapse mechanisms. Fixed-duration dosing with treatment-free intervals is being explored to improve safety, efficacy, and reduce healthcare burden.
Data Highlights
Characteristic
Value
Number of patients
23
Median age (range)
68 years (28–92)
Female
52%
High-risk cytogenetics
10/23 (43%)
Median prior lines of therapy
4 (range 3–9)
BsAb target
BCMA: 20; GPRC5D: 3
Best response prior to discontinuation
CR/sCR: 16; VGPR: 6; PR: 1
Median duration of bsAb treatment
7.6 months (range 1–52)
Most common discontinuation cause
Infection (12 patients)
Median follow-up from discontinuation
15.5 months (range 3–32.3)
Progression-free survival at 6 months
90.5% (95% CI, 78.8–100)
Progression-free survival at 12 months
84.0% (95% CI, 68.7–100)
Progression-free survival at 18 months
70.0% (95% CI, 46.4–100)
Key Findings
Among 23 patients who discontinued bsAb without progression, 82.6% remained alive and progression-free at median 15.5 months follow-up.
Most patients (16/23) had achieved complete or stringent complete response prior to discontinuation.
Infections were the leading cause of treatment discontinuation (12/23 patients).
Patients treated with GPRC5D-targeting bsAb (3 patients) remained in remission up to 25.5 months post-discontinuation.
Four patients relapsed after discontinuation, with a median time to relapse of 7.3 months; two had high-risk cytogenetics.
Post-relapse treatments varied, with only one patient achieving a subsequent complete response.
Clinical Implications
Fixed-duration bispecific antibody therapy may offer durable remission in heavily pre-treated relapsed/refractory MM patients while potentially reducing risks associated with continuous dosing such as T-cell exhaustion and infections. This approach could improve patient quality of life and reduce healthcare costs. Clinicians should consider fixed-duration regimens and monitor for relapse, especially in patients with high-risk cytogenetics.
Conclusion
Limited-duration bispecific antibody treatment in relapsed/refractory multiple myeloma can achieve long-lasting remissions in a majority of patients, supporting further prospective evaluation of fixed-duration dosing strategies.
