Phase 2 study of two sequential three-drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma.

Novel sequential combination therapy for induction may improve the quality of response and therefore prolong survival in newly diagnosed multiple myeloma (MM) patients. We report results from a phase 2 study of two sequential three-drug combinations. Forty-four previously untreated, symptomatic MM patients received: bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11), cyclophosphamide 300 mg/m(2) (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21-day cycles, followed by bortezomib 1.0 mg/m(2), dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%>/= very good partial response. Twenty-two patients have undergone stem-cell transplantation. After a median follow-up of 20.9 months, five patients have died; none was induction therapy-related. Median event-free survival (EFS) and overall survival (OS) have not been reached; estimated 1-year EFS and OS rates were 81% and 91% respectively. Both three-drug combinations were well tolerated; 82% of patients completed all six cycles. Toxicities were predictable and manageable; the most-commonly reported grade 3/4 toxicity was neuropathy (11%). This novel sequential three-drug combination therapy is effective and well-tolerated in previously untreated MM patients.