Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405)

Abstract

Rituximab, bortezomib, modified hyper-cyclophosphamide, doxorubicin, vincristine, dexamethasone (VcR-CVAD) induction chemoimmunotherapy and maintenance rituximab (MR) were evaluated for efficacy and safety in Eastern Cooperative Oncology Group protocol E1405. Patients with previously untreated mantle cell lymphoma received VcR-CVAD chemotherapy every 21 days for 6 cycles, followed by MR for 2 years. Transplant-eligible patients had the option of autologous stem cell transplantation (ASCT) consolidation instead of MR. The primary end point was the complete response (CR) rate to VcR-CVAD. The secondary end points were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Seventy-five eligible patients with a median age of 62 (range 40-76) were enrolled. The ORR was 95% and a CR was achieved in 68% of patients. After a median follow-up of 4.5 years, 3-year PFS and OS were 72% and 88%, respectively. No substantial difference in PFS or OS was observed between patients treated with MR (n = 44) vs ASCT (n = 22). There were no unexpected toxicities. VcR-CVAD produced high ORR and CR rates in mantle cell lymphoma. MR after VcR-CVAD induction performed similarly to ASCT and may improve response duration. Randomized clinical trials comparing MR against ASCT should be considered and randomized clinical trials evaluating bortezomib's contribution to conventional therapy are under way. This study was registered at www.clinicaltrials.gov as #NCT00433537.

Figures

Figure 1

Treatment plan for VcR-CVAD induction and MR. G-CSF, granulocyte colony-stimulating factor.

Figure 2

Throughput of patients enrolled in E1405. *Includes 1 patient who received ASCT after 1 cycle of MR.

Figure 3

PFS. (A) PFS from study entry in all eligible patients (n = 75). The median follow-up for PFS is 3.1 years. (B) PFS from start of MR/ASCT by subgroups receiving MR (n = 44) vs ASCT (n = 22). The median follow-up for PFS is 3.4 years for the MR group and 2.6 years for the ASCT group.

Figure 4

OS. (A) OS from study entry in all eligible patients (n = 75). (B) OS from start of MR/ASCT by subgroups receiving MR (n = 44) vs ASCT (n = 22).

Figure 5

Schema of E1411. Maintenance therapy is administered for 2 years. B, bendamustine; R, rituximab; V, bortezomib.