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Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.

Zweegman, Sonja; van der Holt, Bronno; Mellqvist, Ulf-Henrik; Salomo, Morten; Bos, Gerard M J; Levin, Mark-David; Visser-Wisselaar, Heleen; Hansson, Markus LU ; van der Velden, Annette W G and Deenik, Wendy, et al. (2016) In Blood 127(9). p.1109-1116
Abstract
The combination of melphalan, prednisone and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma (NDMM) who are ineligible for stem-cell transplantation. Long term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone and lenalidomide, followed by lenalidomide maintenance therapy showed promising results, without severe neuropathy emerging. We randomly assigned 668 NDMM patients, ineligible for stem-cell transplantation, between nine 4-weekly cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label,... (More)
The combination of melphalan, prednisone and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma (NDMM) who are ineligible for stem-cell transplantation. Long term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone and lenalidomide, followed by lenalidomide maintenance therapy showed promising results, without severe neuropathy emerging. We randomly assigned 668 NDMM patients, ineligible for stem-cell transplantation, between nine 4-weekly cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomised phase 3 trial was undertaken by HOVON and the NMSG. The primary endpoint was progression-free survival (PFS). The accrual for the study was completed in October 19, 2012. 318 patients were randomly assigned to receive MPT-T and 319 MPR-R. After a median follow up of 36 months PFS with MPT-T was 20 months (95% CI 18-23 months) versus 23 months (95% CI 19-27 months) with MPR-R (HR 0.87 [0.72-1.04], p=0.12). Response rates were similar, with ≥VGPR 47% and 45% respectively. Hematological toxicity was more pronounced with MPR-R, especially grade 3 and 4 neutropenia: 64 versus 27%. Neuropathy ≥ grade 3 was significantly higher in the MPT-T arm; 16% versus 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 versus 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance versus myelosuppression with MPR. (Less)
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@article{1686aaa9-7dd3-458b-9214-7ca95c1b0f0e,
  abstract     = {The combination of melphalan, prednisone and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma (NDMM) who are ineligible for stem-cell transplantation. Long term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone and lenalidomide, followed by lenalidomide maintenance therapy showed promising results, without severe neuropathy emerging. We randomly assigned 668 NDMM patients, ineligible for stem-cell transplantation, between nine 4-weekly cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomised phase 3 trial was undertaken by HOVON and the NMSG. The primary endpoint was progression-free survival (PFS). The accrual for the study was completed in October 19, 2012. 318 patients were randomly assigned to receive MPT-T and 319 MPR-R. After a median follow up of 36 months PFS with MPT-T was 20 months (95% CI 18-23 months) versus 23 months (95% CI 19-27 months) with MPR-R (HR 0.87 [0.72-1.04], p=0.12). Response rates were similar, with ≥VGPR 47% and 45% respectively. Hematological toxicity was more pronounced with MPR-R, especially grade 3 and 4 neutropenia: 64 versus 27%. Neuropathy ≥ grade 3 was significantly higher in the MPT-T arm; 16% versus 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 versus 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance versus myelosuppression with MPR.},
  author       = {Zweegman, Sonja and van der Holt, Bronno and Mellqvist, Ulf-Henrik and Salomo, Morten and Bos, Gerard M J and Levin, Mark-David and Visser-Wisselaar, Heleen and Hansson, Markus and van der Velden, Annette W G and Deenik, Wendy and Gruber, Astrid and Coenen, Juleon L L M and Plesner, Torben and Klein, Saskia K and Tanis, Bea C and Szatkowski, Damian L and Brouwer, Rolf E and Westerman, Matthijs and Leys, M Rineke B L and Sinnige, Harm A M and Haukås, Einar and van der Hem, Klaas G and Durian, Marc F and Mattijssen, E Vera J M and van de Donk, Niels W C J and Stevens-Kroef, Marian J P L and Sonneveld, Pieter and Waage, Anders},
  issn         = {1528-0020},
  language     = {eng},
  number       = {9},
  pages        = {1109--1116},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.},
  url          = {http://dx.doi.org/10.1182/blood-2015-11-679415},
  volume       = {127},
  year         = {2016},
}