Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial

Sara Bringhen, Mattia D'Agostino, Laura Paris, Stelvio Ballanti, Norbert Pescosta, Stefano Spada, Sara Pezzatti, Mariella Grasso, Delia Rota-Scalabrini, Luca De Rosa, Vincenzo Pavone, Giulia Gazzera, Sara Aquino, Marco Poggiu, Armando Santoro, Massimo Gentile, Luca Baldini, Maria Teresa Petrucci, Patrizia Tosi, Roberto MarascaClaudia Cellini, Antonio Palumbo, Patrizia Falco, Roman Hájek, Mario Boccadoro, Alessandra Larocca

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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.

Original languageEnglish
JournalHaematologica
DOIs
Publication statusE-pub ahead of print - Oct 3 2019

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    Bringhen, S., D'Agostino, M., Paris, L., Ballanti, S., Pescosta, N., Spada, S., Pezzatti, S., Grasso, M., Rota-Scalabrini, D., De Rosa, L., Pavone, V., Gazzera, G., Aquino, S., Poggiu, M., Santoro, A., Gentile, M., Baldini, L., Petrucci, M. T., Tosi, P., ... Larocca, A. (2019). Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial. Haematologica. https://doi.org/10.3324/haematol.2019.226407