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

Abstract

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.

• Authors: 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 Marasca, Claudia Cellini, Antonio Palumbo, Patrizia Falco, Roman Hájek, Mario Boccadoro, Alessandra Larocca
• Journal: Haematologica (Haematologica) Vol. 105 Issue 7 Pg. 1937-1947 (07 2020) ISSN: 1592-8721 [Electronic] Italy
• PMID: 31582542 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2020 Ferrata Storti Foundation.

Chemical References

• Dexamethasone
• Lenalidomide
• Melphalan
• Prednisone

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Dexamethasone (therapeutic use)
• Disease-Free Survival
• Humans
• Lenalidomide (therapeutic use)
• Maintenance Chemotherapy
• Melphalan (therapeutic use)
• Multiple Myeloma (diagnosis, drug therapy)
• Prednisone (therapeutic use)
• Progression-Free Survival
• Treatment Outcome