Comparing first-line treatment combinations with and without maintenance therapy

This study compared first-line treatment options for multiple myeloma with and without maintenance therapy. Researchers reported superior treatment outcomes with high-dose melphalan (Alkeran) plus stem cell transplantation when compared to a combination of orally administered treatments. Additional maintenance therapy with lenalidomide (Revlimid) reduced disease progression in both groups.

Standard treatment for multiple myeloma involves high doses of chemotherapy and replacing blood-forming cells destroyed by the cancer treatment with a stem cell transplant. Not all patients are able to undergo a stem cell transplant. MPR is treatment combination commonly prescribed for patients not eligible to undergo stem cell transplantation. This is a combination of the chemotherapy drug melphalan, the steroid drug prednisone (Deltasone), and the biologic drug lenalidomide.

Many patients eventually relapse after stem cell transplantation. This is because high-dose chemotherapy is unlikely to be able to target all myeloma cells. Maintenance therapy after transplantation can reduce the risk of relapse. Whether lenalidomide is a suitable maintenance therapy for multiple myeloma after transplantation or MPR is still being investigated.

This study aimed to compare first-line treatment options with and without maintenance therapy.

273 patients with newly diagnosed multiple myeloma were included. Patients were randomly assigned to receive either high-dose melphalan plus stem cell transplantation (melphalan group) or MPR. In the second phase of the study, patients in both groups were further randomly assigned to either receive maintenance therapy with lenalidomide or no maintenance therapy. Treatment outcomes were followed for an average of 51.2 months.

Overall, 237 patients had disease progression or died during the study period. The average time to disease progression was 43 months for patients in the melphalan group. This was significantly longer compared to patients treated with MPR (22.4 months). The 4-year overall survival rate (proportion who have not died from any cause since treatment) was also significantly higher in the melphalan group (81.6%) compared to MPR (65.3%). Age and disease stage did not affect this outcome.

In the second phase of the study, maintenance therapy with lenalidomide significantly improved average time to disease progression (41.9 months) compared to no maintenance therapy (21.6 months). Maintenance therapy reduced the risk of death or disease progression by 53%. This was unaffected by the type of initial treatment received (melphalan group or MPR). No significant differences in 3-year overall survival were observed with the addition of maintenance therapy. It was 88% with maintenance therapy and 79.2% without maintenance therapy.

Very low neutrophil (type of white blood cell) and platelet (blood cells involved in clotting) levels were significantly more common with high-dose melphalan than with MPR. Infection rates were also higher in the melphalan group (16.3%) compared to MPR (0.8%). Patients treated with high-dose melphalan were also more likely to report stomach-related side effects (18.4%) compared to patients receiving MPR (0%). Maintenance therapy with lenalidomide was associated with skin-related side effects as well as low neutrophil levels.

Researchers concluded that high-dose melphalan plus stem cell transplantation was more effective at improving disease progression and survival compared to MPR. However, it was also associated with a higher rate of side effects. Additional maintenance therapy with lenalidomide reduced disease progression in both groups.

Some of the authors are affiliated with manufacturers of the study drugs. The findings from this study are also limited to younger patients (aged 65 years or younger) with newly diagnosed multiple myeloma.