TY - JOUR
T1 - Once-weekly carfilzomib, pomalidomide, and low-dose dexamethasone for relapsed/refractory myeloma
T2 - a phase I/II study
AU - Bringhen, Sara
AU - Mina, Roberto
AU - Cafro, Anna Maria
AU - Liberati, Anna Marina
AU - Spada, Stefano
AU - Belotti, Angelo
AU - Gaidano, Gianluca
AU - Patriarca, Francesca
AU - Troia, Rossella
AU - Fanin, Renato
AU - De Paoli, Lorenzo
AU - Rossi, Giuseppe
AU - Lombardo, Alessandra
AU - Bertazzoni, Paola
AU - Palumbo, Antonio
AU - Sonneveld, Pieter
AU - Boccadoro, Mario
N1 - Funding Information:
Conflict of interest S.B. has received honoraria from Celgene, Janssen, BMS, Amgen; Advisory board for Janssen and Amgen; consultancy fees from Takeda; G.G. has served on the advisory boards for Roche, AbbVie, Janssen, Gilead, and Morphosys; F.P. has received lecturing fees from MSD Italia and served on the advisory board for Janssen; L. D.P. has served on the advisory boards for AbbVie, Amgen, Celgene, and Janssen; G.R. has served on the advisory boards for Celgene and Amgen; A.P. is currently a Takeda employee; P.S. has received research support from Amgen, Celgene, Janssen, Karyopharm, and honoraria from Amgen, Celgene, Janssen, Karyopharm and BMS; and M.B. has received research funding from Amgen, BMS, Celgene, Janssen, Mundipharma, Novartis, Sanofi, and honoraria from AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Sanofi. The remaining authors declare that they have no conflict of interest.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ⩾65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m2. The recommended phase 2 dose was established at 70 mg/m2and 54 patients (phase 1 and 2) received weekly carfilzomib 70 mg/m2: 85% of them achieved ⩾partial response (PR), 66% ⩾very good PR, 30%⩾near-complete response (CR) and 15% CR. Responses improved in 40 patients who started maintenance: 98% achieved ⩾PR, including 29% CR and 10% stringent CR. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 53.2% and 81%, respectively. The most frequent grade 3-5 toxicities were neutropenia (22%) and cardiopulmonary adverse events (9%). This is the first study of weekly carfilzomib plus an alkylating agent in elderly patients with NDMM. wKCyd was effective, with an acceptable risk/benefit ratio, and thus can be a valid option in this setting.Leukemia advance online publication, 22 December 2017; doi:10.1038/leu.2017.327.
AB - This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ⩾65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m2. The recommended phase 2 dose was established at 70 mg/m2and 54 patients (phase 1 and 2) received weekly carfilzomib 70 mg/m2: 85% of them achieved ⩾partial response (PR), 66% ⩾very good PR, 30%⩾near-complete response (CR) and 15% CR. Responses improved in 40 patients who started maintenance: 98% achieved ⩾PR, including 29% CR and 10% stringent CR. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 53.2% and 81%, respectively. The most frequent grade 3-5 toxicities were neutropenia (22%) and cardiopulmonary adverse events (9%). This is the first study of weekly carfilzomib plus an alkylating agent in elderly patients with NDMM. wKCyd was effective, with an acceptable risk/benefit ratio, and thus can be a valid option in this setting.Leukemia advance online publication, 22 December 2017; doi:10.1038/leu.2017.327.
UR - https://www.scopus.com/pages/publications/85042525658
U2 - 10.1038/s41375-018-0024-1
DO - 10.1038/s41375-018-0024-1
M3 - Article
SN - 0887-6924
VL - 32
SP - 1803
EP - 1807
JO - Leukemia
JF - Leukemia
IS - 8
ER -
