Author Affiliations
- Sara Bringhen1,*,
- Mattia D'Agostino1,
- Laura Paris2,
- Stelvio Ballanti3,
- Norbert Pescosta4,
- Stefano Spada1,
- Sara Pezzatti5,
- Mariella Grasso6,
- Delia Rota-Scalabrini7,
- Luca De Rosa8,
- Vincenzo Pavone9,
- Giulia Gazzera1,
- Sara Aquino10,
- Marco Poggiu1,
- Armando Santoro11,
- Massimo Gentile12,
- Luca Baldini13,
- Maria Teresa Petrucci14,
- Patrizia Tosi15,
- Roberto Marasca16,
- Claudia Cellini17,
- Antonio Palumbo1,
- Patrizia Falco18,
- Roman Hájek19,
- Mario Boccadoro1 and
- Alessandra Larocca1
- 1 Division of Hematology, University of Torino,AOU Città della Salute e della Scienza di Torino;
- 2 Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy;
- 3 Ematologia e Immunologia Clinica, O. S. Maria della Misericordia, S. Andrea delle Fratte, Perugia;
- 4 Reparto Ematologia e Centro TMO, Ospedale Centrale, Bolzano, Italy;
- 5 Divisione di Ematologia, Ospedale S. Gerardo, Monza, Italy;
- 6 Azienda Ospedaliera S.Croce-Carle, Cuneo, Italy;
- 7 Medical Oncology, Candiolo Cancer Institute FPO IRCCS, Candiolo, Italy;
- 8 Hematology and Stem Cell Transplantation Unit, Az. Osp. S. Camillo-Forlanini, Rome, Italy;
- 9 UOC Ematologia e trapianto, Az. Osp. C. Panico, Tricase (Lecce), Italy;
- 10 Ematologia, IRCCS Osp. Policlinico S. Martino, Genova, Italy;
- 11 Istituto Clinico Humanitas, Humanitas University, Rozzano-Milano, Italy;
- 12 UOC Ematologia AO Cosenza, Cosenza, Italy;
- 13 Ematologia, Univ. degli Studi di Milano, Fond. IRCCS Ca' Granda,Osp. Maggiore Policlinico, Milano;
- 14 Hematology, Azienda Policlinico Umberto I, Roma, Italy;
- 15 UO Ematologia, Ospedale di Rimini, AUSL della Romagna, Rimini, Italy;
- 16 Hematology, Dpt. of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena,IT;
- 17 U.O. Ematologia, Ospedale Santa Maria delle Croci, Ravenna, Italy;
- 18 SSD Ematologia, ASLTO4, Ospedali di Chivasso Cirié Ivrea, Italy;
- 19 Dpt. of Haematooncology, Univ. Hospital Ostrava / Faculty of Medicine, University of Ostrava, CZ
- ↵* Corresponding author; email: sarabringhen{at}yahoo.com
Abstract
In the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction has been prospectively evaluated in transplant-ineligible multiple myeloma patients. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. This analysis (median follow-up of 71 months) focused on maintenance treatment and on subgroup analyses according to the International Myeloma Working Group Frailty Score. 217 patients in lenalidomide-dexamethasone, 217 in melphalan-prednisone-lenalidomide and 220 in cyclophosphamide-prednisone-lenalidomide arms were evaluable. 284 (43%) patients were fit, 205 (31%) intermediate-fit and 165 (25%) frail. After induction, 402 patients were eligible for maintenance, (lenalidomide arm: 204; lenalidomide-prednisone: 198). After a median duration of maintenance of 22.0 months, progression-free survival from start of maintenance was 22.2 months with lenalidomide-prednisone vs 18.6 months with lenalidomide (HR 0.85,p=0.14), with no differences across frailty subgroups. The most frequent grade ≥3 toxicity was neutropenia (10% of lenalidomide-prednisone and 21% of lenalidomide patients; p=0.001). Grade ≥3 non-hematologic adverse events were rare (<15%). In fit patients, melphalan-prednisone-lenalidomide significantly prolonged progression-free survival compared to cyclophosphamide-prednisone-lenalidomide (HR 0.72,p=0.05) and lenalidomide-dexamethasone (HR 0.72, p=0.04). Likewise, a trend towards a better overall survival was noted for melphalan-prednisone-lenalidomide and cyclophosphamide-prednisone-lenalidomide, as compared to lenalidomide-dexamethasone. No differences were observed in intermediate-fit and frail patients. This analysis showed positive outcomes of maintenance with lenalidomide-based regimens, with a good safety profile. For the first time, we showed that fit patients benefit from a triplet full-dose regimen, while intermediate-fit and frail patients from gentler regimens. ClinicalTrials.gov registration number: NCT01093196.
- Received May 20, 2019.
- Accepted September 26, 2019.
- Copyright © 2019, Ferrata Storti Foundation