Comparative efficacy of talquetamab vs. real-world physician's choice of treatment in triple-class-exposed relapsed/refractory multiple myeloma: updated analyses of MonumenTAL-1 vs. LocoMMotion/MoMMent

Introduction: Talquetamab, a bispecific antibody targeting GPRC5D, is approved for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) based on results from MonumenTAL-1. We report updated indirect comparisons of talquetamab vs. real-world physician's choice of treatment (RWP...

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Autores: Einsele, Hermann, Moreau, Philippe, Bahlis, Nizar, Bhutani, Manisha, Viencent, Laure, Karlin, Lionel, Perrot, Aurore, Goldschmidt, Hartmut, Van de Donk, Niels W. C. J., Ocio San Miguel, Enrique María|||0000-0002-5765-0085, Martínez López, Joaquín, Rodríguez-Otero, Paula, Dytfeld, Dominik, Jakubowiak, Andrzej, Schinke, Carolina, Besemer, Britta, Anguille, Sébastien, Manier, Salomon, Rasche, Leo, Teipel, Rapahel
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/38764
Acceso en línea:https://hdl.handle.net/10902/38764
Access Level:acceso abierto
Palabra clave:LocoMMotion
MoMMent
MonumenTAL-1
Talquetamab
Triple-class exposed relapsed/refractory multiple myeloma
Descripción
Sumario:Introduction: Talquetamab, a bispecific antibody targeting GPRC5D, is approved for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) based on results from MonumenTAL-1. We report updated indirect comparisons of talquetamab vs. real-world physician's choice of treatment (RWPC) in patients with TCE RRMM. Methods: External control arms were created for three MonumenTAL-1 cohorts, two without prior T cell redirection (TCR) therapies who received subcutaneously administered talquetamab 0.4 mg/kg weekly (QW; n = 143) or 0.8 mg/kg every other week (Q2W; n = 154) and one with prior B cell maturation antigen (BCMA) TCR (n = 75) who received either schedule (median follow-up [mFU] 38.2, 31.2, and 30.3 months, respectively), from two real-world studies, LocoMMotion (mFU 26.4 months) and MoMMent (mFU 27.1 months). Imbalances in baseline covariates were adjusted using inverse probability weighting and multivariable regression. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), very good partial response (VGPR) rate, and complete response (CR) rate; odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional-hazards model. Results: In the TCR-naïve cohort, talquetamab Q2W had significantly improved outcomes vs. RWPC; RRs were ORR, 2.58; VGPR, 5.01; CR, 52.22 and HRs were DOR, 0.52 (p = 0.0011); PFS, 0.47; TTNT, 0.46; OS, 0.35 (all p < 0.0001). Results were similar in the QW cohort. The prior TCR cohort had favorable outcomes with talquetamab vs. RWPC; RRs were ORR, 3.03; VGPR, 4.88 and HRs were DOR, 0.09, (p = 0.0004); PFS, 0.30 (p < 0.0001); TTNT, 0.26 (p < 0.0001) and OS, 0.37 (p = 0.0020). Conclusion: With longer follow-up, these comparative analyses further demonstrate the clinical benefit of talquetamab over RWPC in patients with TCE RRMM, irrespective of prior TCR therapy.