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

Sonja Zweegman, Bronno van der Holt, Ulf-Henrik Mellqvist, Morten Salomo, Gerard M J Bos, Mark-David Levin, Heleen Visser-Wisselaar, Markus Hansson, Annette W G van der Velden, Wendy Deenik, Astrid Gruber, Juleon L L M Coenen, Torben Plesner, Saskia K Klein, Bea C Tanis, Damian L Szatkowski, Rolf E Brouwer, Matthijs Westerman, M Rineke B L Leys, Harm A M Sinnige & 8 andre Einar Haukås, Klaas G van der Hem, Marc F Durian, E Vera J M Mattijssen, Niels W C J van de Donk, Marian J P L Stevens-Kroef, Pieter Sonneveld, Anders Waage

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma 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 patients between nine 4-week 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, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 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 vs myelosuppression with MPR.

OriginalsprogEngelsk
TidsskriftBlood
Vol/bind127
Udgave nummer9
Sider (fra-til)1109-16
ISSN0006-4971
DOI
StatusUdgivet - 3. mar. 2016

Fingeraftryk

Melphalan
Prednisone
Confidence Intervals
Disease-Free Survival
Maintenance
Hematology
Neutropenia

Citer dette

Zweegman, S., van der Holt, B., Mellqvist, U-H., Salomo, M., Bos, G. M. J., Levin, M-D., ... Waage, A. (2016). Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood, 127(9), 1109-16. https://doi.org/10.1182/blood-2015-11-679415
Zweegman, Sonja ; van der Holt, Bronno ; Mellqvist, Ulf-Henrik ; Salomo, Morten ; Bos, Gerard M J ; Levin, Mark-David ; Visser-Wisselaar, Heleen ; Hansson, Markus ; van der Velden, Annette W G ; Deenik, Wendy ; Gruber, Astrid ; Coenen, Juleon L L M ; Plesner, Torben ; Klein, Saskia K ; Tanis, Bea C ; Szatkowski, Damian L ; Brouwer, Rolf E ; Westerman, Matthijs ; Leys, M Rineke B L ; Sinnige, Harm A M ; Haukås, Einar ; van der Hem, Klaas G ; Durian, Marc F ; Mattijssen, E Vera J M ; van de Donk, Niels W C J ; Stevens-Kroef, Marian J P L ; Sonneveld, Pieter ; Waage, Anders. / Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. I: Blood. 2016 ; Bind 127, Nr. 9. s. 1109-16.
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title = "Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma",
abstract = "The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma 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 patients between nine 4-week 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, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95{\%} confidence interval [CI], 18-23 months) vs 23 months (95{\%} CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95{\%} CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47{\%} and 45{\%}, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64{\%} vs 27{\%}. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16{\%} vs 2{\%} in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 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 vs myelosuppression with MPR.",
author = "Sonja Zweegman and {van der Holt}, Bronno and Ulf-Henrik Mellqvist and Morten Salomo and Bos, {Gerard M J} and Mark-David Levin and Heleen Visser-Wisselaar and Markus Hansson and {van der Velden}, {Annette W G} and Wendy Deenik and Astrid Gruber and Coenen, {Juleon L L M} and Torben Plesner and Klein, {Saskia K} and Tanis, {Bea C} and Szatkowski, {Damian L} and Brouwer, {Rolf E} and Matthijs Westerman and Leys, {M Rineke B L} and Sinnige, {Harm A M} and Einar Hauk{\aa}s 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 Pieter Sonneveld and Anders Waage",
note = "{\circledC} 2016 by The American Society of Hematology.",
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doi = "10.1182/blood-2015-11-679415",
language = "English",
volume = "127",
pages = "1109--16",
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Zweegman, S, van der Holt, B, Mellqvist, U-H, Salomo, M, Bos, GMJ, Levin, M-D, Visser-Wisselaar, H, Hansson, M, van der Velden, AWG, Deenik, W, Gruber, A, Coenen, JLLM, Plesner, T, Klein, SK, Tanis, BC, Szatkowski, DL, Brouwer, RE, Westerman, M, Leys, MRBL, Sinnige, HAM, Haukås, E, van der Hem, KG, Durian, MF, Mattijssen, EVJM, van de Donk, NWCJ, Stevens-Kroef, MJPL, Sonneveld, P & Waage, A 2016, 'Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma', Blood, bind 127, nr. 9, s. 1109-16. https://doi.org/10.1182/blood-2015-11-679415

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; van der Velden, Annette W G; Deenik, Wendy; Gruber, Astrid; Coenen, Juleon L L M; Plesner, Torben; Klein, Saskia K; Tanis, Bea C; Szatkowski, Damian L; Brouwer, Rolf E; Westerman, Matthijs; Leys, M Rineke B L; Sinnige, Harm A M; Haukås, Einar; van der Hem, Klaas G; Durian, Marc F; Mattijssen, E Vera J M; van de Donk, Niels W C J; Stevens-Kroef, Marian J P L; Sonneveld, Pieter; Waage, Anders.

I: Blood, Bind 127, Nr. 9, 03.03.2016, s. 1109-16.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

AU - Zweegman, Sonja

AU - van der Holt, Bronno

AU - Mellqvist, Ulf-Henrik

AU - Salomo, Morten

AU - Bos, Gerard M J

AU - Levin, Mark-David

AU - Visser-Wisselaar, Heleen

AU - Hansson, Markus

AU - van der Velden, Annette W G

AU - Deenik, Wendy

AU - Gruber, Astrid

AU - Coenen, Juleon L L M

AU - Plesner, Torben

AU - Klein, Saskia K

AU - Tanis, Bea C

AU - Szatkowski, Damian L

AU - Brouwer, Rolf E

AU - Westerman, Matthijs

AU - Leys, M Rineke B L

AU - Sinnige, Harm A M

AU - Haukås, Einar

AU - van der Hem, Klaas G

AU - Durian, Marc F

AU - Mattijssen, E Vera J M

AU - van de Donk, Niels W C J

AU - Stevens-Kroef, Marian J P L

AU - Sonneveld, Pieter

AU - Waage, Anders

N1 - © 2016 by The American Society of Hematology.

PY - 2016/3/3

Y1 - 2016/3/3

N2 - The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma 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 patients between nine 4-week 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, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 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 vs myelosuppression with MPR.

AB - The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma 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 patients between nine 4-week 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, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 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 vs myelosuppression with MPR.

U2 - 10.1182/blood-2015-11-679415

DO - 10.1182/blood-2015-11-679415

M3 - Journal article

VL - 127

SP - 1109

EP - 1116

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -

Zweegman S, van der Holt B, Mellqvist U-H, Salomo M, Bos GMJ, Levin M-D et al. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016 mar 3;127(9):1109-16. https://doi.org/10.1182/blood-2015-11-679415