A new study from the large Spanish Myeloma Group suggests that patients with newly diagnosed multiple myeloma may best be treated with alternating regimens versus with sequential regimens.
In 231 newly diagnosed, symptomatic elderly patients (median age, 75 years), researchers evaluated the use of sequential regimens versus alternating the use of bortezomib/melphalan/prednisone (VMP) and lenalidomide plus low-dose dexamethasone (Rd) in the GEM2010MAS65 trial. The sequential treatment scheme involved 9 consecutive cycles of VMP followed by 9 consecutive cycles of Rd. The patients treated with the alternating scheme started with 1 cycle of VMP and alternated with 1 cycle of Rd, or started with 1 cycle of Rd and alternated with 1 cycle of VMP, each for up to 18 cycles.
“The hypothesis was that there would be higher efficacy for the alternating scheme, less probability of cell tumor escape, and lower cumulative toxicity,” said Maria-Victoria Mateos, MD, PhD, of the University Hospital of Salamanca, Spain, who presented the findings at the American Society of Hematology annual meeting.
After 9 months of treatment, the response rates were higher with the alternating scheme (93%) than with sequential treatment (89%). The alternating arm also produced a greater proportion of very good partial responses (VGPRs) or better (78% vs 56%, respectively; P = .004) as well as higher complete responses (CRs)/stringent complete responses (sCRs; 41% vs 26%, respectively; P = .02) than the sequential regimen arm after 9 months of treatment, Dr Mateos reported.
After a median of 13 cycles of treatment in the intent-to-treat population, the response rate was 94% with alternating treatments and 79% with the sequential regimens; the rates of VGPR or greater were 69% and 60%, respectively, and the rates of CR/sCR were 46% and 39%, respectively. These differences were not significant.
The progression-free survival (PFS) and overall survival (OS) rates after 20 months of follow-up were not significantly different between the arms, although the rates were numerically higher with the alternating approach (PFS: 84% vs 80%, respectively; OS: 92% vs 88%, respectively).
The study also established the benefit of achieving a CR or sCR. For patients achieving this level of response, the PFS rates were 96% in the alternating arm and 92% in the sequential arm, which was significantly better than that observed among patients with less than a VGPR, whose PFS rates at 20 months were 78% and 62%, respectively, Dr Mateos reported.
Improved Outcomes
The toxicity profiles after 9 cycles among 87 patients in the sequential arm and 86 patients in the alternating arm were slightly, but not significantly, better. There were 183 grade 3 to 4 adverse events in the sequential arm and 173 in the alternating arm. The proportions of patients with grade 1 peripheral neuropathy were 32% and 22%, respectively, and the proportions with grade 2 were 14% and 10%, respectively. Discontinuations resulting from toxicity were equal, at approximately 12% per arm.
“After 9 induction cycles, the alternating scheme is superior in efficacy, especially in terms of stringent complete responses and complete responses, as compared with the sequential, and with no more additional toxicity,” Dr Mateos concluded. “The benefit of these combinations seems to be consistent in different risk groups, especially in patients with high-risk cytogenetic abnormalities.”
Dr Mateos suggested that the final benefit of these 2 approaches should not be judged until they are evaluated as part of a total therapy approach in the elderly, which she called “a treatment approach of great value” in this population. Dr Mateos also indicated that the Spanish Myeloma Group will wait for longer follow-up before making the alternating regimen the backbone for clinical trials.