Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909

Abstract

PURPOSE Mantle-cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with a poor prognosis. We explored the feasibility, safety, and effectiveness of an aggressive immunochemotherapy treatment program that included autologous stem-cell transplantation (ASCT) for patients up to age 69 years with newly diagnosed MCL. PATIENTS AND METHODS The primary end point was 2-year progression-free survival (PFS). A successful trial would yield a 2-year PFS of at least 50% and an event rate (early progression plus nonrelapse mortality) less than 20% at day +100 following ASCT. Seventy-eight patients were treated with two or three cycles of rituximab combined with methotrexate and augmented CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). This treatment was followed by intensification with high doses of cytarabine and etoposide combined with rituximab and filgrastim to mobilize autologous peripheral-blood stem cells. Patients then received high doses of carmustine, etoposide, and cyclophosphamide followed by ASCT and two doses of rituximab. Results There were two nonrelapse mortalities, neither during ASCT. With a median follow-up of 4.7 years, the 2-year PFS was 76% (95% CI, 64% to 85%), and the 5-year PFS was 56% (95% CI, 43% to 68%). The 5-year overall survival was 64% (95% CI, 50% to 75%). The event rate by day +100 of ASCT was 5.1%. CONCLUSION The Cancer and Leukemia Group B 59909 regimen is feasible, safe, and effective in patients with newly diagnosed MCL. The incorporation of rituximab with aggressive chemotherapy and ASCT may be responsible for the encouraging outcomes demonstrated in this study, which produced results comparable to similar treatment regimens.

Fig 1.

The throughput of patients enrolled on Cancer and Leukemia Group B (CALGB) 59909. NRM, nonrelapse mortality; ASCT, autologous stem- cell transplantation.

Fig 2.

(A) Progression-free survival and (B) overall survival by intent-to-treat analysis. Patients were censored at the time of last follow-up without an event or at the time of coming off protocol treatment because of denial of insurance for autologous stem-cell transplantation (ASCT), patient refusal of ASCT, or allogeneic stem-cell transplantation. Dotted lines indicate 95% CIs.

Fig A1.

(A) Progression-free survival and (B) overall survival by intent-to-treat analysis, according to patients treated before or after the major protocol amendment involving methotrexate dose and schedule. Patients were censored at the time of last follow-up without an event or at the time of coming off protocol treatment because of denial of insurance for autologous stem-cell transplantation (ASCT), patient refusal of ASCT, or allogeneic stem-cell transplantation. Preamendment is high-dose methotrexate and postamendment is low-dose methotrexate.