The results of two large randomized studies comparing MP to MPT, undertaken after an Italian Phase II of MP plus low-dose thalidomide (MPT) in patients with previously untreated MM demonstrated a remarkable 93% overall response rate (45% CR/nCR),106 have recently reported. Palumbo et al. randomized 255 patients between the ages of 60 and 85 with newly diagnosed MM to either MP or MPT. All patients received six 4-week cycles of MP, and patients randomized to the MPT arm also received thalidomide 100 mg daily until either disease progression or unacceptable toxicity.107 Patients receiving MPT had a superior overall response rate (76% vs 48%), CR/nCR rate (28% vs 7%), and 2-year EFS rate (54% vs 27%; p = 0.0006). Three-year OS was also higher—80% for MPT versus 64% for MP—although this difference did not reach statistical significance. The increased efficacy of MPT came at the price of increased toxicity, particularly infectious and thrombotic complications. The incidence of grade 3-4 nonhematologic adverse events was 48% in the MPT arm, compared to 25% in the MP arm (p = 0.0002). Prior to the introduction of prophylactic enoxaparin, 20% of patients receiving MPT developed deep vein thromboses (DVTs). After enoxa-parin 40 mg subcutaneously once daily was added, the incidence of DVTs dropped to 3%, resulting in an overall incidence of 12% on this trial. The IFM compared MP (12 cycles), MPT (thalidomide < 400 mg/day through the end of MP), and a high-dose melphalan-based regimen (VAD X 2, then cyclophosphamide 3 g/m2 to mobilize stem cells, then MEL(100) with ASCS X 2) in 476 patients between the ages of 65-75 with previously untreated MM.108 The median progression-free survival for MPT was 29 months (compared to 17 months for MP (p < 0.0001) and 19 months for MEL(100) (p = 0.0001)). Median OS, which was 30 months for MP and 39 months for MEL(100), was not reached in the MPT arm after 56 months median follow-up (p = 0.0008 for MPT vs MP, p = 0.014 for MPT vs MEL(100)).

0 0

Post a comment