n the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction therapy was prospectively evaluated in transplant-ineligible patients with multiple myeloma. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. The analysis presented here (median follow-up of 71 months) is focused on maintenance treatment and on subgroup analyses defined according to the International Myeloma Working Group Frailty Score. Of the 654 evaluable patients, 217 were in the lenalidomide-dexamethasone arm, 217 in the melphalan-prednisone-lenalidomide arm and 220 in the cyclophosphamide-prednisone-lenalidomide arm. With regards to the Frailty Score, 284 (43%) patients were fit, 205 (31%) were intermediate-fit and 165 (25%) were frail. After induction, 402 patients were eligible for maintenance therapy (lenalidomide arm, n=204; lenalidomide-prednisone arm, n=198). After a median duration of maintenance of 22.0 months, progression-free survival from the start of maintenance was 22.2 months with lenalidomide-prednisone vs 18.6 months with lenalidomide (hazard ratio 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 (hazard ratio 0.72, P=0.05) and lenalidomide-dexamethasone (hazard ratio 0.72, P=0.04). Likewise, a trend towards a better overall survival was noted for patients treated with melphalan-prednisone-lenalidomide or 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 full-dose triplet regimen, while intermediate-fit and frail patients benefit from gentler regimens. ClinicalTrials.gov registration number: NCT01093196.

Azienda Ospedaliera S Croce Carle Cuneo Italy

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

Divisione di Ematologia Ospedale S Gerardo Monza Italy

Ematologia e Centro Trapianti IRCCS Ospedale Policlinico San Martino Genova Italy

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Hematology and Bone Marrow Transplant Unit Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII Bergamo Italy

Hematology and Stem Cell Transplantation Unit Az Osp S Camillo Forlanini Rome Italy

Hematology Azienda Policlinico Umberto 1 Roma Italy

Hematology Unit Department of Medical and Surgical Sciences University of Modena and Reggio Emilia Modena Italy

Istituto Clinico Humanitas Humanitas University Rozzano Milano Italy

Medical Oncology Candiolo Cancer Institute FPO IRCCS Candiolo Italy

Myeloma Unit Division of Hematology University of Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Torino Italy

Reparto Ematologia e Centro TMO Ospedale Centrale Bolzano Italy

Sezione di Ematologia e Immunologia Clinica Ospedale Santa Maria della Misericordia località Sant'Andrea delle Fratte Perugia Italy

SSD Ematologia ASLTO4 Ospedali di Chivasso Cirié Ivrea Italy

U O Ematologia Ospedale Santa Maria delle Croci Ravenna Italy

UO Ematologia Ospedale di Rimini AUSL della Romagna Rimini Italy

UOC Ematologia AO Cosenza Cosenza Italy

UOC Ematologia e Trapianto Az Osp C Panico Tricase Italy

UOC Ematologia Università degli Studi di Milano Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Italy

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Octogenarian newly diagnosed multiple myeloma patients without geriatric impairments: the role of age >80 in the IMWG frailty score

Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

Lenalidomide Maintenance with or without Prednisone in Newly Diagnosed Myeloma Patients: A Pooled Analysis

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ClinicalTrials.gov
NCT01093196