A trial of melphalan (Alkeran)/prednisone plus thalidomide in newly diagnosed elderly patients with multiple myeloma suggests that the oral regimen should be the reference treatment for patients in this population who are ineligible for high-dose therapy, according to Thierry Facon, MD, Inter-Groupe Francophone du Myelome (IFM), Lille, France.
ATLANTA-A trial of melphalan (Alkeran)/prednisone plus thalidomide in newly diagnosed elderly patients with multiple myeloma suggests that the oral regimen should be the reference treatment for patients in this population who are ineligible for high-dose therapy, according to Thierry Facon, MD, Inter-Groupe Francophone du Myelome (IFM), Lille, France.
The standard for multiple myeloma patients older than 65 years has been oral melphalan and prednisone (MP), Dr. Facon said at the 47th Annual Meeting of the American Society of Hematology (abstract 780). Based on the notion that adding oral thalidomide to MP (MP-T) may provide increased antitumor benefit and better survival, Dr. Facon and IFM associates conducted the IFM 99-06 trial.
The trial included three arms: MP, MP-T, and an additional well-recognized regimen for this population, intermediate-dose melphalan (MEL100) plus autologous peripheral blood stem cell transplant. Patients randomized to MEL100 received two courses of VAD (vincristine, Adriamycin, and dexamethasone), cyclophosphamide with G-CSF support, two courses of melphalan (100 mg/m2), and stem cell transplant with G-CSF support. MEL100 has been shown to improve survival in patients aged 50 to 70 (Palumbo et al, Blood 104:3052-3057, 2004). The primary objective was to compare overall survival between MP and the MP-T and MEL100 arms.
After a second planned interim analysis, the Data Safety and Monitoring Board recommended a third interim analysis at a median follow-up of 32 months with 436 patients enrolled (MP = 191, MP-T = 124, MEL100 = 121). Forty-one percent of patients were age 70 years or older. In the MEL100 treatment group, 6% did not receive VAD, 20% did not receive cyclophosphamide, and 37% did not receive both programmed MEL100 courses.
Responses were more frequent in the MP-T and MEL100 arms (see Table). Progression-free survival was significantly longer for MP-T (median 29.5 months) than for MP (17.2 months, P < .0001) or MEL100 (19.0 months, P = .0001). Similarly, the primary endpoint of overall survival favored MP-T (median not reached at 56 months) over MP (30.3 months, HR 1.9 vs MP-T, P = .0008) and over MEL100 (38.6 months, HR 1.7, P = .014). Overall and progression-free survival rates for MP and MEL100 were not significantly different.
Dr. Facon concluded, "IFM 99-06 results show the superiority of MP-T in the treatment of newly diagnosed elderly patients with multiple myeloma." He said that because MP-T superiority was unequivocal, enrollment was stopped after this third interim analysis.
Deaths and toxicities were generally similar between arms, with severe infections and neutropenia higher in the MEL100 arm. There were no toxic deaths during the 154 MEL100 courses delivered. Neuropathy was reported in 30% of MP-T patients.
Dr. Facon expressed enthusiasm for the MP-T regimen's better outcomes with oral administration. "This is extremely exciting for patients and physicians, as transplantation is a difficult and challenging therapy." He noted that while some issues remain unresolved regarding thalidomide dosing and toxicity, MP-T should be regarded as the reference treatment for newly diagnosed elderly patients ineligible for high-dose therapy.