Continuous lenalidomide treatment for newly diagnosed multiple myeloma

TY - JOUR

T1 - Continuous lenalidomide treatment for newly diagnosed multiple myeloma

AU - Palumbo, Antonio

AU - Hajek, Roman

AU - Delforge, Michel

AU - Kropff, Martin

AU - Petrucci, Maria Teresa

AU - Catalano, John

AU - Gisslinger, Heinz

AU - Wiktor-Jędrzejczak, Wiesław

AU - Zodelava, Mamia

AU - Weisel, Katja

AU - Cascavilla, Nicola

AU - Iosava, Genadi

AU - Cavo, Michele

AU - Kloczko, Janusz

AU - Bladé, Joan

AU - Beksac, Meral

AU - Spicka, Ivan

AU - Plesner, Torben

AU - Radke, Joergen

AU - Langer, Christian

AU - Ben Yehuda, Dina

AU - Corso, Alessandro

AU - Herbein, Lindsay

AU - Yu, Zhinuan

AU - Mei, Jay

AU - Jacques, Christian

AU - Dimopoulos, Meletios A

AU - MM-015 Investigators

PY - 2012/5/10

Y1 - 2012/5/10

N2 - BACKGROUND: Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma.METHODS: We randomly assigned patients who were ineligible for transplantation to receive MPR-R (nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [152 patients]) or to receive MPR (153 patients) or MP (154 patients) without maintenance therapy. The primary end point was progression-free survival.RESULTS: The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P<0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P=0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P=0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP.CONCLUSIONS: MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.).

AB - BACKGROUND: Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma.METHODS: We randomly assigned patients who were ineligible for transplantation to receive MPR-R (nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [152 patients]) or to receive MPR (153 patients) or MP (154 patients) without maintenance therapy. The primary end point was progression-free survival.RESULTS: The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P<0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P=0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P=0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP.CONCLUSIONS: MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.).

KW - Administration, Oral

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Disease-Free Survival

KW - Double-Blind Method

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Induction Chemotherapy

KW - Kaplan-Meier Estimate

KW - Lenalidomide

KW - Maintenance Chemotherapy

KW - Male

KW - Melphalan

KW - Multiple Myeloma

KW - Neoplasms, Second Primary

KW - Neutropenia

KW - Prednisone

KW - Thalidomide

KW - Clinical Trial, Phase III

KW - Comparative Study

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1056/NEJMoa1112704

DO - 10.1056/NEJMoa1112704

M3 - SCORING: Journal article

C2 - 22571200

VL - 366

SP - 1759

EP - 1769

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 19

ER -