Randomized phase II study of weekly carfilzomib 70 mg/m2 and dexamethasone with or without cyclophosphamide in relapsed and/or refractory multiple myeloma patients
Puertas, Borja (Hospital Universitario de Salamanca)
González-Calle, Verónica (Hospital Universitario de Salamanca)
Sureda, Anna (Institut Català D'Oncologia L'Hospitalet)
Moreno, María José (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Oriol, Albert (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
González, Esther (Hospital Universitario de Cabueñes (Gijón))
Rosiñol, Laura (Hospital Clínic i Provincial de Barcelona)
López, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Escalante, Fernando (Hospital Universitario de León (Lleó))
Martínez-Lopez, Joaquín F. (Hospital Universitario 12 de Octubre (Madrid))
Carrillo, Estrella (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Clavero, Esther (Hospital Universitario Virgen De Las Nieves (Granada, Andalusia))
Ríos-Tamayo, Rafael (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Rey-Búa, Beatriz (Hospital Universitario de Salamanca)
González-Rodríguez, Ana P. (Hospital Universitario Central De Asturias)
Dourdil, Victoria (Hospital Clínico Universitario Lozano Blesa (Saragossa))
De Arriba, Felipe (Instituto Murciano de Investigación Biosanitaria)
González, Sonia (Complexo Hospitalario Universitario De Santiago)
Perez de Oteyza, Jaime (Hospital Universitario Madrid Sanchinarro (Madrid))
Hernández, Miguel Teodoro (Hospital Universitario De Canarias)
García-Mateo, Aránzazu (Hospital General de Segovia)
Bargay Lleonart, Joan (Hospital Universitario Son Llàtzer)
Bladé, Joan (Hospital Clínic i Provincial de Barcelona)
Lahuerta, Juan José (Hospital 12 de Octubre (Madrid))
San Miguel, Jesús Fernando (Clínica Universidad de Navarra (Pamplona, Navarra))
Ocio, Enrique M. (Universidad De Cantabria)
Mateos, M. V (Hospital Universitario de Salamanca)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m, 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/m 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/m was safe and convenient, and, overall, the toxicity was manageable in both arms.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Haematologica, Vol. 108 Núm. 10 (october 2023) , p. 2753-2763, ISSN 1592-8721

DOI: 10.3324/haematol.2022.282490
PMID: 37102598

11 p, 986.1 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles