Among patients with newly diagnosed multiple myeloma who were eligible for stem-cell transplantation, progression-free survival was significantly longer for those who received standard high-dose melphalan than for those who received melphalan/prednisone/lenalidomide as consolidation therapy in an open-label, phase III, randomized trial, investigators reported online Sept. 4 in the New England Journal of Medicine.
This finding confirms that high-dose melphalan "remains the more effective therapeutic option" in this patient population, said Dr. Antonio Palumbo, chief of the myeloma unit at the University of Turin, Italy, and his associates.
In addition, maintenance therapy with lenalidomide, as compared with no maintenance therapy, also significantly extended progression-free survival. The optimal combination of these approaches – high-dose melphalan plus stem-cell transplantation followed by lenalidomide maintenance – yielded a 5-year progression-free survival of approximately 48% and an overall survival of 78%, the investigators noted.
Dr. Palumbo and his associates performed this industry-sponsored trial at 62 medical centers in Italy and Israel. A total of 399 patients aged 65 years and younger underwent induction therapy (lenalidomide plus dexamethasone) and received cyclophosphamide and granulocyte colony-stimulating factor to mobilize stem cells. The 273 study participants who then entered the consolidation phase of treatment were randomly assigned to receive either standard high-dose melphalan plus stem-cell transplantation (141 patients) or melphalan/prednisone/lenalidomide (MPR) plus stem-cell transplantation (132 patients).
The 251 participants who remained in the trial after stem-cell transplantation were then randomly assigned to receive no maintenance therapy (125 patients) or lenalidomide maintenance therapy (126 patients) until disease progressed or they developed unacceptable adverse effects. At the end of the study, 237 patients had disease progression or had died, 45 were still receiving lenalidomide maintenance therapy, and 24 were not receiving maintenance therapy.
After a median follow-up of 51 months (range, 1-66 months), the primary end point – progression-free survival – was 54.7 months for high-dose melphalan plus lenalidomide maintenance, 37.4 months for high-dose melphalan without maintenance therapy, 34.2 months for MPR plus lenalidomide maintenance, and 21.8 months for MPR without maintenance therapy. The respective 5-year overall survival rates were 78.4%, 66.6%, 70.2%, and 58.7%, the investigators said (N. Engl. J. Med. 2014;371:895-905).
Both hematologic and nonhematologic adverse events were more frequent with high-dose melphalan than with MPR. The most concerning were neutropenia and infections. "However, toxic effects were manageable and did not affect the rate of early death or treatment discontinuation, or patients’ ability to proceed to the maintenance phase," Dr. Palumbo and his associates said.
In addition, "the rate of second primary cancers was low, and no between-group differences were reported," they said.
Celgene funded this trial but was not involved in data collection or analysis. Dr. Palumbo reported receiving fees from Celgene, Amgen, and other companies, and his associates reported ties to numerous industry sources.