Chemotherapy and stem-cell transplant for multiple myeloma remain superior

1. Patients with multiple myeloma treated with high-dose chemotherapy and autologous stem-cell transplantation consolidation therapy had significantly longer disease-free survival, overall survival, and hematologic adverse events compared to those treated with a combination of melphalan, prednisone, and lenalidomide.

2. Patients treated with lenalidomide maintenance therapy had a significantly longer disease-free survival but not a significantly improved overall survival compared to patients treated with no maintenance therapy.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The current standard of therapy for newly diagnosed multiple myeloma in patients under 65 years of age is high-dose chemotherapy plus autologous stem-cell transplantation. This regimen has been shown to prolong progression-free survival and overall survival in these patients. Given the recent success of immunomodulatory drugs in treating patients with multiple myeloma, there has been growing interest in comparing the standard treatment to the newer and less toxic, oral medications.

In this open-label, randomized study, patients under 65 years of age with newly diagnosed multiple myeloma were treated with one of two consolidation therapies: high-dose melphalan plus autologous stem-cell transplantation or a combination of melphalan-prednisone-lenalidomide (MPR). Patients in the high-dose chemotherapy and stem-cell transplant group had significantly longer progression-free survival and improved 4-year overall survival, but also had significantly higher numbers of adverse events including neutropenia, thrombocytopenia, and infections. The authors also compared maintenance therapy with lenalidomide versus no maintenance therapy and found that the former group had a significantly longer progression-free survival, though there was no significant difference in overall survival rates. There were also significantly higher levels of adverse events including neutropenia and infections in the lenalidomide maintenance therapy group.

The greatest strength of this study is the use of a well-powered randomized study design to address an important clinical question in the management of newly diagnosed multiple myeloma. Major drawbacks include the fact that only 68% of the originally enrolled subjects were eligible for randomization to the consolidation therapy groups, largely due to inadequate induction therapy responses. This means that the final study population is biased towards patients with treatment-responsive multiple myeloma. Secondly, the study does not address the efficacy of bortezomib, a proteasome inhibitor that has shown utility in the treatment of multiple myeloma.

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“In the era of novel, effective agents, autologous stem cell transplantation confirmed its superiority over chemotherapy with novel agents in young patients (< 65 years of age) with multiple myeloma, prolonging both progression-free survival and overall survival. Therefore, transplantation should be used at diagnosis, and not delayed until relapse as is currently done in several centers.

In addition, maintenance therapy with lenalidomide further improved progression-free survival and marginally overall survival. Thus, the optimal strategy for young patients is a sequential approach that includes induction with novel agents, followed by transplantation and then maintenance therapy.”