Real‑world matched comparison of talquetamab versus teclistamab in Relapsed/Refractory multiple myeloma

Abstract Introduction Teclistamab is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, and the first among bispecific antibodies to be approved while talquetamab is an anti-CD3 and anti-GPRC5D bispecific humanized monoclonal antibody for the treatment of patients that have relapsed/refractory multiple myeloma (RRMM). Direct head-to-head analysis of these two drugs with real-world data is limited. We compared the effectiveness and safety of talquetamab and teclistamab in propensity-matched RRMM cohorts. Methods Data for adults with RRMM receiving talquetamab or teclistamab between 25 Oct 2022 and 1 Jan 2025 were extracted from the US Collaborative Network of TriNetX. After exclusions, 229 talquetamab and 643 teclistamab patients were identified; 1:1 propensity-score matching (age, sex, race, comorbidities, renal function, prior therapies) yielded 198 well-balanced patients in both arms. Outcomes were evaluated from day +1 to day +365. Primary endpoints were all-cause mortality and multiple-myeloma (MM) remission. The assessed key secondary endpoints were cytokine release syndrome (CRS), sepsis, pneumonia, thrombocytopenia, hepatotoxicity, immune effector cell–associated neurotoxicity (ICANS), grade ≥3 neutropenia and lymphopenia and acute kidney injury. Moreover, the risk ratios (RR) and hazard ratios (HR) were calculated with 95% confidence intervals (CI). The significance value was set as p<0.05. Results Both of the considered cohorts were comparable. The median age was 67 years and 56% of the total were male participants. For talquetamab, the median follow-up period was 6.1 months (IQR 9.0), while it was 6.2 months (IQR 9.3) for teclistamab. Moreover, in comparison to the cohort of patients on teclistamab that had 42 deaths, 35 deaths were recorded in the talquetamab cohort. Similarly, the 1-year mortality was 21.2% for the former against 17.7% for the latter (RR 0.83, 95 % CI 0.56–1.25; HR 0.87, 95 % CI 0.55–1.36; log-rank p = 0.53). Moreover, MM remission was recorded in 28.3% patients (56/198), as compared to 30.8% (61/198) (RR 0.92, 95 % CI 0.68–1.25; p = 0.58); remission curves overlapped with HR 0.93; log rank p = 0.69. The safety outcomes were also rather similar. Any-grade CRS occurred in 22 out of 104 (21.2%) talquetamab-treated cases, while 21 out of 151 (13.9%) teclistamab-treated patients exhibited it (RR 1.52, 95 % CI 0.88–2.62; p = 0.13); all events were ≤grade 2. ICANS occurred in 9.9% versus 7.4% (RR 1.34; p = 0.42). Grade ≥3 neutropenia was more common with talquetamab (53/198, 26.8 %) than it was with teclistamab (38/198, 19.2 %) and correlated with shorter neutropenia-free survival (HR 1.53, 95 % CI 1.01–2.32; log rank p = 0.04). Severe lymphopenia was recorded in 10 patients per arm (5.1% each). Earlier onset was seen in talquetamab recipients, thus showing a HR of 3.54 (log rank p = 0.04). Furthermore, the incidence of infectious complications favoured talquetamab numerically, with sepsis being 10.1 % versus 13.6 % (RR 0.74; p = 0.28) and pneumonia 15.7 % versus 21.2 % (RR 0.74; p = 0.15). No cases of hepatotoxicity were observed and thrombocytopenia rates were also comparable. Finally, acute kidney injury occurred in 21.7% versus 30.3% (RR 0.72; p = 0.05). Conclusions Within this real-world matched analysis, talquetamab and teclistamab provided similar early survival and remission outcomes for RRMM, with broadly overlapping toxicity profiles. Talquetamab was associated with higher early-onset neutropenia yet showed numerically fewer serious infections, whereas CRS and ICANS remained low-grade for both agents. Bispecific antibody selection decision should weigh in baseline marrow reserve and infection risk until longer follow-up clarifies durability and late-onset toxicities.