MM-263: Reduced-Frequency Dosing of FDA-Approved Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma: A Systematic Review of Maintaining Efficacy While Reducing Infection-Related Toxicity
Year: 2026
Type: conference-abstract
Abstract: Background: Bispecific antibodies (BsAbs) targeting BCMA (teclistamab, elranatamab) and GPRC5D (talquetamab) have transformed relapsed/refractory multiple myeloma (RRMM), achieving overall response rates (ORR) of 61–70% in heavily pretreated patients. However, standard weekly dosing is associated with grade ≥3 infections in 45–55% of recipients, driven by prolonged hypogammaglobulinemia and T‑cell exhaustion. Emerging evidence suggests that reducing dosing frequency to every 2 or 4 weeks after deep response may preserve efficacy while curbing infectious toxicity. Objective: To systematically evaluate whether reduced‑frequency dosing (Q2W or Q4W) of FDA‑approved BsAbs in RRMM maintains clinical efficacy compared with standard weekly dosing, and to quantify the associated reduction in infection‑related adverse events. Methods: A PRISMA‑guided systematic review was conducted. PubMed, Embase, Scopus, Cochrane CENTRAL, Web of Science, and major hematology conference proceedings (ASH, ASCO, EHA, SOHO; 2022–2026) were searched. Included were prospective trials, cohort studies, and post hoc analyses reporting reduced-frequency BSAb dosing in adults with RRMM. Primary efficacy outcomes were ORR, progression‑free survival (PFS), and response maintenance after dose reduction. Secondary outcomes were grade ≥3 infections, hypogammaglobulinemia, and treatment discontinuation. Risk of bias was assessed using the ROBINS-I and the Newcastle-Ottawa Scale. Narrative synthesis was performed due to heterogeneity. Results: Fourteen studies (three pivotal trials with de‑escalation cohorts, six real‑world studies, five sub‑analyses) comprising >1,200 patients were included. For teclistamab, transition from weekly to Q2W after ≥6 months of complete response (CR) preserved responses in 100% (37/37) of patients (MajesTEC‑1). Real-world data showed comparable median PFS between the weekly and reduced-frequency groups (9.1 vs 11.3 months; p=0.141), despite lower dose intensity. All-grade infections declined from 6.08 to 2.25 per patient-year with Q2W dosing. For elranatamab, Q4W maintenance after ≥6 cycles of Q2W maintained responses in 92.6% (25/27) of patients at 6 months, with grade 3–4 infections decreasing from 17.9% to 10.7% after Q4W transition (Pfizer, 2025). For talquetamab, the FDA-approved Q2W primary schedule (0.8 mg/kg) achieved an ORR of 71% and a median PFS of 11.2 months, with grade ≥3 infections at 21%, substantially lower than those observed with BCMA-targeted agents (Chari et al., 2025). Across all agents, no study reported loss of response attributable to dose de‑escalation, but selection bias limits causal inference. Conclusion: Reduced‑frequency dosing (Q2W or Q4W) of teclistamab, elranatamab, and talquetamab in RRMM patients who have achieved deep, sustained responses preserves efficacy while substantially lowering infection rates. These findings support regulatory approvals for biweekly and monthly maintenance schedules. However, the evidence remains derived from non-randomized, single-arm cohorts with a moderate risk of bias. Prospective randomized trials are urgently needed to define optimal de-escalation timing, patient selection biomarkers, and comparative value against fixed-duration CAR T therapy.
Institution: CHI St. Vincent
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204691393