Sequential Targeting in Multiple Myeloma: Talquetamab, a GPRC5D bispecific antibody, as a Bridge to BCMA CAR-T cell therapy.

作者：B. Dhakal, O. Akhtar, D. Fandrei, Alexandria M. Jensen, R. Banerjee, Darren Pan, S. Richard, Reed Friend, Matthew J. Rees, Patrick Costello, M. V. Vazquez Martinez, O. Pasvolsky, Charlotte B. Wagner, James A. Davis, O. C. Castaneda Puglianini, Ran Reshef, A. Afrough, D. Dima, M. Bhutani, Omar Nadeem, Ricardo D. Parrondo, Ciara L. Freeman, Lekha Mikkilineni, S. Raza, Larry D. Anderson, P. Kapoor, H. Hosoya, Saurabh Chhabra, A. Grajales-Cruz, Mahmoud R. Gaballa, S. Midha, M. Alsina, D. Sborov, Krina K. Patel, Yi Lin, Christopher J. Ferreri, N. Gagelmann, A. Kumar, Doris K. Hansen, Andrew J Cowan, Luciano J. Costa, M. Merz, S. Sidana · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2025029773 · 被引用次数：30 · 研究领域：Medicine

Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), two BCMA-directed chimeric antigen receptor T cell (CAR-T) therapies, have transformed outcomes for relapsed/refractory multiple myeloma (RRMM); however, the 6-8 weeks manufacturing time risks disease progression or death in up to 10% of patients, highlighting the need for effective bridging strategies. Talquetamab, a GPRC5D-targeting bispecific antibody, represents a promising option. We performed a multi-institutional retrospective analysis across 20 centers (18 US, 2 Germany) evaluating talquetamab as a bridging therapy prior to cilta-cel or ide-cel. Among 134 patients receiving talquetamab, 119 proceeded to CAR-T (n=98 cilta-cel, n=21 ide-cel). Reasons for not proceeding (n=15) included progression (n=7), manufacturing failure (n=6), or patient decision (n=2). Median age was 65 years; patients had received a median 5 prior lines of therapy. High-risk cytogenetics and extramedullary disease were present in 44% and 41% respectively. Notably, 85% would not have met CARTITUDE-1/KarMMa eligibility criteria. Talquetamab was administered for a median 23 days (82% at 0.8 mg/kg biweekly). Toxicity was manageable: no grade ≥3 CRS, 2% grade 3 ICANS and grade 1-2 Talq unique toxicities (70% oral, 38% skin, 17% nail; 60% resolved). Talquetamab achieved 71% response rate. Post CAR-T 88% responded (54% complete response), with low-grade toxicities (2 grade≥3 CRS, 1 grade 3 ICANS and 5% grade≥3 infections). Two c...