Updated GEM2005 Trial Confirms Benefit of Melphalan/Bortezomib Combination in Elderly Multiple Myeloma Patients


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Melphalan in combination with bortezomib (Velcade) should be maintained as one of the standards of care for the treatment of elderly patients with multiple myeloma, concluded Spanish trialists reporting updated results from the GEM2005 study comparing bortezomib/melphalan/prednisone with bortezomib/thalidomide (Thalomid)/prednisone as induction therapy.

Previously reported results showed that newly diagnosed elderly multiple myeloma patients receiving bortezomib/melphalan/prednisone had slightly longer progression-free and overall survival and reduced frequency of side effects. “However, this conclusion was based on a relatively short median follow-up of 32 months,” Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca/IBSAL, and colleagues wrote in Blood. “We now provide an update of this phase 3 randomized trial after a median follow-up of 6 years, confirming the role of the alkylator as part of bortezomib-based combinations for transplant-ineligible [multiple myeloma] patients.”

Study Details

A total of 260 patients in 63 Spanish centers were randomly assigned to receive 6 cycles of bortezomib/melphalan/prednisone or bortezomib/thalidomide/prednisone as induction therapy; those who completed induction therapy were randomly assigned to maintenance therapy with bortezomib/thalidomide or bortezomib/prednisone.

Patients in the bortezomib/melphalan/prednisone arm had a median progression-free survival of 32 months compared with 23 months for the bortezomib/thalidomide/prednisone arm (P = .09). Treatment with bortezomib/melphalan/prednisone resulted in a significant improvement in overall survival compared with bortezomib/thalidomide/prednisone (median of 63 and 43 months, respectively; hazard ratio [HR] = 0.67, P = .01).

Achieving complete response and immunophenotypic complete response was associated with a significantly longer overall survival, especially in the bortezomib/melphalan/prednisone arm, where 66% remain alive after 8 years, stated the authors.

Value of Prolonged Treatment in Elderly Patients

Bortezomib/melphalan/prednisone demonstrated superior progression-free survival in both the group of patients between 65 and 75 years (31 vs 27 months for bortezomib/melphalan/prednisone and bortezomib/thalidomide/prednisone, respectively) and the group of patients older than 75 years (32 months vs 18 months; HR = 1.6, 95% CI = 1.1–2.5, P =.04).

Median overall survival for patients between 65 and 75 years was 66 months for those receiving bortezomib/melphalan/prednisone vs 50 months for those receiving bortezomib/thalidomide/prednisone. For patients older than 75 years, median overall survival was 51 months for those receiving bortezomib/melphalan/prednisone vs 34 months for those receiving bortezomib/thalidomide/prednisone (HR = 1.7, 95% CI = 1.1–2.9, P = .02).

“Our study has two major findings,” the investigators concluded. “First, melphalan remains an important and cost-effective drug for the treatment of newly diagnosed elderly myeloma patients, and second, the value of prolonged treatment and depth of response in elderly patients is confirmed.” ■

The trial is registered with www.ClinicalTrials.gov (NCT00443235).

Mateos M, et al: Blood. September 18, 2014 (early release online).



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