Talquetamab targets a G protein-coupled receptor (GPRC5D), and teclistamab targets B-cell maturation antigen (BCMA). The phase 2 RedirecTT-1 study (NCT04586426) tested the combination of these two agents in patients with true EMD myeloma (n=90) [1]. The primary endpoint was the overall response rate (ORR). “All patients were triple-class refractory and the majority of them had received at least 5 prior therapies (56.7%),” added Dr Shaji Kumar (Mayo Clinic, MN, USA).
The ORR was 78.9%, and 54.4% of the participants achieved at least a complete response. These rates were fairly consistent across participants who had received prior CAR T-cell therapies or bispecific antibodies. “The combination therapy almost doubles the ORR of the individual monotherapies, and many participants had deeper responses than with either talquetamab or teclistamab alone,” said Dr Kumar. He emphasised that 66.2% of the responders were still on therapy at the data cut-off point, with a median follow-up of 13.4 months. The estimated progression-free survival and overall survival rates at 1 year were 61% and 74.5%, respectively. Furthermore, the occurrence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) was consistent with the occurrence of these events on the respective monotherapies. In total, 77.8% of the study population had CRS, all of which were grade 1 or 2, and 12.2% experienced ICANS, with 1 case of grade 3 and 1 case of grade 4. “We only had 5 patients discontinuing the trial due to adverse events,” said Dr Kumar.
“Results from the RedirecTT-1 trial showed that the combination of talquetamab and teclistamab can deliver deep and durable responses in patients with true EMD myeloma, a population with a significant unmet need,” concluded Dr Kumar.
- Kumar S, et al. Phase 2 study of talquetamab plus teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: RedirecTT-1. LB4001, EHA2025 Congress, 12–15 June, Milan, Italy.
Medical writing support was provided by Robert van den Heuvel.
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