Randomized phase II study of weekly carfilzomib 70 mg/m2 and dexamethasone with or without cyclophosphamide in relapsed and/or refractory multiple myeloma patients

Autor: Borja Puertas, Verónica González-Calle, Anna Sureda, María José Moreno, Albert Oriol, Esther González, Laura Rosiñol, Jordi López, Fernando Escalante, Joaquín Martínez-Lopez, Estrella Carrillo, Esther Clavero, Rafael Ríos-Tamayo, Beatriz Rey-Bua, Ana Pilar González-Rodríguez, Victoria Dourdil, Felipe de Arriba, Sonia González, Jaime Pérez-de-Oteyza, Miguel T. Hernández, Aránzazu García-Mateo, Joan Bargay, Joan Bladé, Juan José Lahuerta, Jesús F. San Miguel, Enrique M. Ocio, María-Victoria Mateos
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Haematologica, Vol 108, Iss 10 (2023)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2022.282490
Popis: In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone (KCd) was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PL). One hundred and ninety-seven patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PL was one (range, 1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, approximetely 70% to immunomodulators, and approximetely 50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomide-refractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 versus 11.3 months (hazard ratio =1.7, 95% confidence interval: 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PL, but a significant benefit in PFS was observed with the triplet combination in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.
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