Comparative real-world outcomes with talquetamab and teclistamab in relapsed/refractory multiple myeloma: A TriNetX observational study.

Abstract

e19519 Background: Talquetamab (GPRC5D) and teclistamab (BCMA) are bispecific antibodies for relapsed/refractory multiple myeloma (RRMM), but comparative real-world evidence is limited. We compared 1-year effectiveness and safety outcomes between talquetamab and teclistamab. Methods: We conducted a retrospective cohort study in the TriNetX US Collaborative Network. Adults (≥18 years) with RRMM treated with talquetamab or teclistamab from October 2022–November 2025 were included. Patients with solitary plasmacytoma, plasma cell leukemia, or clinical trial–only monitoring codes were excluded. Cohorts were propensity score matched 1:1 on demographics and comorbidities (198 per group). Outcomes through 365 days post-index included all-cause mortality, remission, immune/hematologic toxicities, infections, and organ complications. Effect estimates included risk difference (RD), risk ratio (RR), hazard ratio (HR), 95% confidence intervals (CI), and log-rank p values. Results: Among 1,626 eligible RRMM patients, 402 received talquetamab and 1,224 received teclistamab prior to matching. After matching, baseline characteristics were balanced (mean age 66.8 years; 42% female; similar comorbidity profiles). Grade 3 neutropenia was more common with talquetamab (25.8%) than teclistamab (19.7%) (RD 0.061, 95% CI −0.014 to 0.136; RR 1.31, 95% CI 0.96–1.79; HR 1.46, 95% CI 0.99–2.15; log-rank p=0.054). Grade 3 lymphopenia incidence was similar (5.6% vs 5.1%) (RD 0.005, 95% CI −0.034 to 0.044; RR 1.10, 95% CI 0.55–2.20; HR 1.28, 95% CI 0.63–2.61; log-rank p=0.49). Acute kidney injury was numerically higher with teclistamab (29.3% vs 22.2%) (RD −0.071, 95% CI −0.154 to 0.012; RR 0.76, 95% CI 0.56–1.04; HR 0.77, 95% CI 0.54–1.10; log-rank p=0.15). Mortality (18.2% vs 20.7%; HR 0.91; log-rank p=0.61) and remission (29.1% vs 31.6%; HR 0.95; log-rank p=0.74) were similar between talquetamab and teclistamab. Cytokine release syndrome occurred more often with talquetamab (20.2% vs 14.6%; HR 1.49; log-rank p=0.17). Neurotoxicity was comparable (9.6% vs 7.9%; HR 1.24; log-rank p=0.52). Pneumonia (16.2% vs 20.3%) and sepsis (10.6% vs 13.1%) were numerically lower with talquetamab; thrombocytopenia and hepatotoxicity were similar. Conclusions: In this real-world propensity-matched RRMM cohort, talquetamab and teclistamab had comparable 1-year mortality and remission, with differing toxicity profiles. Talquetamab was associated with higher grade 3 neutropenia and numerically higher cytokine release syndrome, whereas teclistamab showed a signal toward more acute kidney injury and higher infection rates. These data may support individualized treatment selection based on toxicity risk.