ATLANTA—Adding bortezomib to thalidomide maintenance therapy after stem-cell transplantation for multiple myeloma (MM) significantly prolongs progression-free survival (PFS), according to a randomized Phase 3 study presented during the 54th American Society of Hematology (ASH) Annual Meeting and Exposition.

Bortezomib plus thalidomide maintenance, “resulted in a significantly longer PFS when compared to thalidomide alone or with single-agent α2-interferon with no increased toxicity,” reported coauthor Juan-José Lahuerta MD, of the Hospital 12 de Octubre, in Madrid, Spain.

“However, the addition of bortezomib did not overcome the poor impact of high-risk cytogenetics,” the coauthor cautioned.

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The phase 3 study by the Spanish Myeloma Group (PETHEMA/GEM) enrolled 266 patients, diagnosed with MM during 2007-2011. Patients were randomized to receive one of three maintenance therapies after stem-cell transplantation: thalidomide+ bortezomib (TV, n=89; thalidomide 100 mg daily plus 1 cycle of bortezomib at 1.3 mg/m2 on Days 1, 4, 8 and 11, every 3 months); thalidomide alone (T, n=87; 100 mg daily), or subcutaneous α2-IFN (n=90; 3 MU, 3 times per week). Each arm had “similarly distributed” patient ages, M-protein types, ISS stages, cytogenetics and extramedullary plasmacytomas, Dr. Lahuerta noted.

The response status at the time of randomization for maintenance after ASCT was CR: 51%, nCR: 12%, PR: 34%, MR: 2% and SD: 1%, and was well balanced in the three groups, Dr. Lahuerta reported.

Maintenance therapy continued for 3 years or until disease progression or toxicity precluded further treatment. Responses, relapses and progressions were monitored using EBMT criteria under contract with an outside research organization and then centrally reassessed.

After a median follow-up period of 34.9 months, PFS was longer among patients receiving maintenance TV than those undergoing T or α2-IFN (P=0.0009), but overall survival (OS) did not differ significantly between the different maintenance therapy arms (P=0.47), according to the study authors.

The CR rate with maintenance was improved by 21% with TV, 15% with T and 15% with α2-IFN, with no significant difference between the treatment arms. Grade 3/4 hematological toxicity was similar between maintenance treatment arms, except in the case of thrombocytopenia (TV vs T: 10% vs 2%; P=0.01), Dr. Lahuerta reported. Grade 3 peripheral neuropathy was absent among patients receiving α2-IFN, but occurred in 15% of TV-treated patients and 14% of T-treated patients; no patients in any arm of the study experienced Grade 4 peripheral neuropathy.

Progression-related discontinuation rates were  17% for TV vs 23% for T vs 35% for α2-IFN, Dr. Lahuerta reported. Discontinuation due to toxicity tended to be more common in thalidomide-arm patients than in those treated with TV (33% vs 18%, P=0.02).

Patients with high-risk cytogenetics [t(4;14), t(14;16) and/or del 17p] had a trend towards a shorter PFS (P=0.11) and a significantly shorter OS (P=0.03), Dr. Lahuerta noted.