Haematologica (Apr 2023)

Randomized phase II study of weekly carfilzomib 70 mg/m<sup>2</sup> and dexamethasone with or without cyclophosphamide in relapsed and/or refractory multiple myeloma patients

  • 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

DOI
https://doi.org/10.3324/haematol.2022.282490
Journal volume & issue
Vol. 108, no. 10

Abstract

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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.