Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma

Valeria Magarotto, Sara Bringhen, Massimo Offidani, Giulia Benevolo, Francesca Patriarca, Roberto Mina, Antonietta Pia Falcone, Lorenzo De Paoli, Giuseppe Pietrantuono, Silvia Gentili, Caterina Musolino, Nicola Giuliani, Annalisa Bernardini, Concetta Conticello, Stefano Pulini, Giovannino Ciccone, Vladimír Maisnar, Marina Ruggeri, Renato Zambello, Tommasina Guglielmelli, Antonio Ledda, Anna Marina Liberati, Vittorio Montefusco, Roman Hajek, Mario Boccadoro and Antonio Palumbo

Key Points

  • Triplet lenalidomide-based regimens did not induce any advantage over doublet lenalidomide-based regimens in elderly myeloma patients.


Lenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple myeloma patients. We randomly assigned 662 patients who were age ≥65 years or transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus low-dose dexamethasone (Rd). The primary end point was progression-free survival (PFS) in triplet (MPR and CPR) vs doublet (Rd) lenalidomide-containing regimens. After a median follow-up of 39 months, the median PFS was 22 months for the triplet combinations and 21 months for the doublet (P = .284). The median overall survival (OS) was not reached in either arms, and the 4-year OS was 67% for the triplet and 58% for the doublet arms (P = .709). By considering the 3 treatment arms separately, no difference in outcome was detected among MPR, CPR, and Rd. The most common grade ≥3 toxicity was neutropenia: 64% in MPR, 29% in CPR, and 25% in Rd patients (P < .0001). Grade ≥3 nonhematologic toxicities were similar among arms and were mainly infections (6.5% to 11%), constitutional (3.5% to 9.5%), and cardiac (4.5% to 6%), with no difference among the arms. In conclusion, in the overall population, the alkylator-containing triplets MPR and CPR were not superior to the alkylator-free doublet Rd, which was associated with lower toxicity. This study was registered at as #NCT01093196.

  • Submitted August 4, 2015.
  • Accepted December 15, 2015.
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