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

Abstract

Summary 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/m2 (days 1, 4, 8, 11), cyclophosphamide 300 mg/m2 (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21‐day cycles, followed by bortezomib 1·0 mg/m2, 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.

Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study

“…These response rates appeared to be comparable to or somewhat higher than those reported in recent studies of the three-drug combinations VDR (ORR 100%),10 lenalidomide, cyclophosphamide and dexamethasone (RCd, ORR: 83%),13 VDC (ORR 84–88%),12,14 and VDC (three cycles) followed by bortezomib, thalidomide and dexamethasone (VTD; three cycles) (ORR 95%) in newly diagnosed MM patients 27. Stringent CR rates and durability data have not yet been reported for all these studies.…”

A comparison of bortezomib, cyclophosphamide, and dexamethasone (Vel-CD) chemotherapy without and with thalidomide (Vel-CTD) for the treatment of relapsed or refractory multiple myeloma

“…Published trials of bortezomib in combination with corticosteroids and/or cytotoxic agents in patients with relapsed or refractory MM reported ORR as high as 60-90%, indicating that bortezomib's activity is substantially improved through the use of combination therapy [10][11][12][13][14]. Induction therapy with bortezomib, cyclophosphamide, and dexamethasone in newly diagnosed MM showed 77-88% of ORR [15][16][17] and showed 75-90% of ORRs as a salvage therapy in patients with MM [14,18]. Reports on four drug combinations such as bortezomib, thalidomide, steroid, and alkylating agents also demonstrated the effectiveness of combination salvage therapy with 67-88% of ORRs [13,19].…”

Bortezomib for the Treatment of Previously Untreated Multiple Myeloma

“…After a median follow-up of 20.9 months, median eventfree survival (EFS) and OS were not reached; estimated 1-year EFS and OS rates were 81 and 91% respectively, revealing a promising option in the optimization of sequential treatment [80]. n Stem cell collection after bortezomib-based induction regimens The effect of bortezomib on the ability to collect stem cells has been examined in the context of Phase II and III trials described above [14,56,61,[64][65][66]68].…”