Reduced-Frequency Dosing of FDA-Approved Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma: A Systematic Review of Maintaining Efficacy While Reducing Infection- Related Toxicity

Why It Matters

Lowering infection risk without sacrificing tumor control could broaden bispecific antibody use and improve quality of life for heavily pre‑treated myeloma patients. The findings also inform regulatory and payer decisions as the field weighs bispecifics against CAR‑T therapies.

Key Takeaways

• Biweekly or monthly dosing maintains response rates in >90% of RRMM patients
• Infection‑related grade ≥3 events drop by up to 40% with reduced frequency
• Median progression‑free survival remains comparable between standard and de‑escalated schedules
• Evidence derives mainly from non‑randomized cohorts; randomized trials are needed
• FDA now supports biweekly/monthly maintenance for BCMA and GPRC5D bispecifics

Pulse Analysis

Bispecific antibodies have quickly become a cornerstone for patients with relapsed/refractory multiple myeloma (RRMM) who have exhausted conventional options. Agents such as teclistamab, elranatamab, and talquetamab target BCMA or GPRC5D and generate overall response rates exceeding 60%, yet the standard weekly administration schedule has been linked to severe infections in 45‑55% of recipients. The toxicity stems from prolonged hypogammaglobulinemia and T‑cell exhaustion, prompting clinicians to explore whether less frequent dosing could preserve the deep responses while mitigating adverse events.

The systematic review, covering literature from 2022‑2026, pooled data from pivotal trials, real‑world cohorts, and sub‑analyses, totaling over 1,200 RRMM patients. Transitioning teclistamab to a biweekly regimen after six months of complete response retained responses in every patient studied and reduced all‑grade infections from 6.08 to 2.25 per patient‑year. Elranatamab’s shift to monthly dosing after six cycles maintained a 92.6% response rate and cut grade ≥3 infections from 17.9% to 10.7%. Talquetamab, already approved on a Q2W schedule, showed an ORR of 71% with a comparatively lower infection profile than BCMA‑targeted agents. Across agents, progression‑free survival remained statistically similar between standard and de‑escalated groups, suggesting that dose reduction does not compromise disease control.

These findings have immediate practical implications. By lowering infection risk, clinicians can keep patients on effective therapy longer, potentially improving overall survival and quality of life. However, the current evidence base is limited to single‑arm and retrospective analyses, underscoring the need for prospective randomized trials to define optimal de‑escalation timing, identify biomarkers for patient selection, and compare bispecific maintenance against fixed‑duration CAR‑T approaches. As regulators begin to endorse biweekly and monthly maintenance schedules, the oncology community must balance enthusiasm with rigorous data to ensure that reduced‑frequency dosing becomes a validated standard of care.