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 Marasca, Claudia Cellini, Antonio Palumbo, Patrizia Falco, Roman Hájek, Mario Boccadoro, Alessandra Larocca
Haematologica October 2019 : haematol.2019.226407; doi:10.3324/haematol.2019.226407

Author Affiliations

  1. Sara Bringhen1,*,
  2. Mattia D'Agostino1,
  3. Laura Paris2,
  4. Stelvio Ballanti3,
  5. Norbert Pescosta4,
  6. Stefano Spada1,
  7. Sara Pezzatti5,
  8. Mariella Grasso6,
  9. Delia Rota-Scalabrini7,
  10. Luca De Rosa8,
  11. Vincenzo Pavone9,
  12. Giulia Gazzera1,
  13. Sara Aquino10,
  14. Marco Poggiu1,
  15. Armando Santoro11,
  16. Massimo Gentile12,
  17. Luca Baldini13,
  18. Maria Teresa Petrucci14,
  19. Patrizia Tosi15,
  20. Roberto Marasca16,
  21. Claudia Cellini17,
  22. Antonio Palumbo1,
  23. Patrizia Falco18,
  24. Roman Hájek19,
  25. Mario Boccadoro1 and
  26. Alessandra Larocca1
  1. 1 Division of Hematology, University of Torino,AOU Città della Salute e della Scienza di Torino;
  2. 2 Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy;
  3. 3 Ematologia e Immunologia Clinica, O. S. Maria della Misericordia, S. Andrea delle Fratte, Perugia;
  4. 4 Reparto Ematologia e Centro TMO, Ospedale Centrale, Bolzano, Italy;
  5. 5 Divisione di Ematologia, Ospedale S. Gerardo, Monza, Italy;
  6. 6 Azienda Ospedaliera S.Croce-Carle, Cuneo, Italy;
  7. 7 Medical Oncology, Candiolo Cancer Institute FPO IRCCS, Candiolo, Italy;
  8. 8 Hematology and Stem Cell Transplantation Unit, Az. Osp. S. Camillo-Forlanini, Rome, Italy;
  9. 9 UOC Ematologia e trapianto, Az. Osp. C. Panico, Tricase (Lecce), Italy;
  10. 10 Ematologia, IRCCS Osp. Policlinico S. Martino, Genova, Italy;
  11. 11 Istituto Clinico Humanitas, Humanitas University, Rozzano-Milano, Italy;
  12. 12 UOC Ematologia AO Cosenza, Cosenza, Italy;
  13. 13 Ematologia, Univ. degli Studi di Milano, Fond. IRCCS Ca' Granda,Osp. Maggiore Policlinico, Milano;
  14. 14 Hematology, Azienda Policlinico Umberto I, Roma, Italy;
  15. 15 UO Ematologia, Ospedale di Rimini, AUSL della Romagna, Rimini, Italy;
  16. 16 Hematology, Dpt. of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena,IT;
  17. 17 U.O. Ematologia, Ospedale Santa Maria delle Croci, Ravenna, Italy;
  18. 18 SSD Ematologia, ASLTO4, Ospedali di Chivasso Cirié Ivrea, Italy;
  19. 19 Dpt. of Haematooncology, Univ. Hospital Ostrava / Faculty of Medicine, University of Ostrava, CZ
  1. ↵* 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.
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Keywords

multiple myeloma
elderly patients
lenalidomide based induction
lenalidomide based maintenance
newly diagnosed
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