Melphalan-Prednisone-Thalidomide (MP-T) Demonstrates a Significant Survival Advantage in Elderly Patients ≥75 Years with Multiple Myeloma Compared with Melphalan-Prednisone (MP) in a Randomized, Double-Blind, Placebo-Controlled Trial, IFM 01/01.

Background: The MP-T combination has become the standard treatment for newly diagnosed MM patients (pts) aged 65 to 75 years (Facon et al; Lancet 2007 [Epub ahead of print]). However, no specific therapeutic recommendation exists for pts ≥75 years regarding the benefit of adding thalidomide to MP. Patients older than 75 years have frequently been excluded from large clinical trials, although they represent more than 20% of MM pts.

Methods: The IFM 01-01 trial was initiated in 4/2002. Pts ≥75 years with untreated MM were randomized to receive MP-placebo (M [0.2mg/kg/d] + P [2 mg/kg/d day1–4]) x 12 courses every 6-weeks + placebo) or MP-T (MP + daily thalidomide [100mg/d]). No anti-VTE prophylaxis was given. The primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS), response to treatment, and toxicity. Trial enrollment was prospectively planned for 258 patients. Two interim analyses were performed after inclusion of 150 and 200 patients. The IFM board decided to stop enrollment after the second interim analysis.

Results: In all, 232 pts were randomized and 3 failed to meet inclusion criteria. In all, 229 pts were analyzed (113 MP-T; 116 MP-placebo) with a median age of 78.5 years (36% ≥80years). No differences between the 2 groups for baseline characteristics were observed except for gender (p=0.03). Data were analysed on an intent-to-treat basis. The median follow-up time was 24 months. The median OS time (se) was 45.3 (1.6) months with MP-T vs 27.7 (2.1) months with MP-placebo, the benefit was significant (p=0.03 log-rank test). The median PFS time (se) was 24.1 (2) months with MP-T vs 19 (1.4) months with MP-placebo (p=0.001). Rates of at least partial response, very good partial response and complete response were 62%, 22% and 7% with MP-T vs 31%, 7% and 1% with MP-placebo, respectively (p<0.001). In the MP-T arm, 42% of pts stopped treatment due to toxicity vs 11% in the MP-placebo arm. The major reasons in the MP-T arm were peripheral neuropathy (12/48), neutropenia (7/48), and DVT (7/48). Some toxicities (Grade 2–4) were significantly increased with MP-T: peripheral neuropathy (20% vs 5%), neutropenia (23% vs 9%) depression (7% vs 2%). There were no significative differences in DVT rates for MP-T (6%) vs MP-placebo (4%) or somnolence (6% vs 3%, respectively). After relapse in the MP-placebo arm, 77% of patients received Thalidomide. Survival time after progression was similar in the 2 groups, 9.8 months after MP-placebo and 9.3 months after MP-T.

Conclusion: These results confirm the superiority of MP-T over MP for prolonging OS in elderly patients with newly diagnosed MM. The toxicity was acceptable in this very elderly population ≥ 75 years. A new era of progress is opened for these very elderly patients.