Individualized Treatment Scheduling and Dose Intensity for Bispecific Antibodies in Heavily Pretreated RRMM With Poor Performance Status: A Real-World Study.
Materials and Methods/Case Presentation/Objective: We retrospectively evaluated consecutive patients with RRMM treated with talquetamab, elranatamab, or teclistamab at a single hematology center. During ongoing treatment, inter-dose intervals and dose intensity were pre-planned and individualized according to patient-related clinical characteristics rather than modified reactively following toxicity. Baseline characteristics, prior treatment exposure, planned inter-dose interval extensions, dose reductions, response, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), grade ≥3 infections, and treatment discontinuation were analyzed. Responses were assessed according to International Myeloma Working Group criteria.
Results/Description/Main Outcome Measure(s):
Fifteen patients received talquetamab (n=9), elranatamab (n=4), or teclistamab (n=2). Median age was 73 years (range, 56-80), and all patients had an ECOG performance status ≥2, including five (33.3%) with ECOG 3-4. Seven patients (46.7%) were classified as frail and six (40.0%) as intermediate-fit. Patients had received a median of four prior lines of therapy (range, 1-8); all were triple-refractory, eight (53.3%) were penta-refractory, and six (40.0%) had prior BCMA-directed exposure. All were CAR T-cell-naïve.
A planned extension of the interval between treatment doses was implemented in seven patients (46.7%), corresponding to a median planned delay of 14 days (range, 10-15). Six patients (40.0%) received a dose reduction, while five (33.3%) underwent both inter-dose interval extension and dose reduction. The overall response rate was 73.3% (11/15), including stringent complete response in three, complete response in three, and partial response in five patients. Responses ≥VGPR were achieved in 40.0% (6/15). Among patients with ECOG 3-4, the response rate was 40.0% (2/5).
Any-grade CRS occurred in five patients (33.3%); only one experienced grade 2 CRS, with no grade ≥3 events. One patient developed grade 1 ICANS, and three experienced a grade ≥3 infection. Five patients discontinued treatment. Median follow-up was five months.
Conclusion(s).: Individualized treatment scheduling and dose reduction were feasible and associated with encouraging early clinical activity and manageable toxicity in this heavily pretreated real-world RRMM cohort, including patients with poor performance status and frailty. Planned extension of inter-dose intervals and dose reductions may facilitate bispecific antibody delivery beyond conventional trial populations. Longer follow-up and larger cohorts are required to confirm response durability and survival outcomes.
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