Mantle cell lymphoma, an aggressive form of B-cell non-Hodgkin lymphoma, has been associated with a poor prognosis and a median overall survival of 3 to 4 years. A study reported at the 52nd American Society of Hematology (ASH) Annual Meeting demonstrated that the addition of high-dose cytarabine to induction chemotherapy that includes R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone) improved outcomes compared with six courses of R-CHOP and chemoradiotherapy when given prior to autologous stem cell transplantation (ASCT) in younger patients with newly diagnosed mantle cell lymphoma.¹

At the time of the ASH meeting, the primary endpoint of the trial-time to treatment failure-had not been reached in the high-dose cytarabine arm (which also included cytarabine in the transplant conditioning regimen). Time to treatment failure was 49 months in the R-CHOP arm. Overall survival was similar between the two arms, and median survival had not yet been reached. Both arms had comparable safety.

"Results of this study confirm that there is a new standard of care for the treatment of younger patients with previously untreated mantle cell lymphoma," commented lead author Olivier ­Hermine, MD, PhD, who is Professor and Head of the Hematological Department at Necker Hospital in Paris. "High-dose cytarabine should be part of induction therapy along with R-CHOP prior to autologous stem-cell transplant, in order to improve outcomes without increased toxicity," he said.

Study Rationale and Design

The European MCL Network initiated the present study to evaluate the superiority of a high-dose cytarabine-containing regimen with R-CHOP and R-DHAP vs R-CHOP followed by chemoradiotherapy and ASCT. The study was conducted in four European countries and randomly assigned 497 patients to treatment for newly diagnosed mantle cell lymphoma from July 2004 to May 2010; 391 patients were evaluable for the primary analysis. Patients were randomly assigned to the control arm (six courses of R-CHOP followed by myeloablative chemoradiotherapy and ASCT) or the experimental arm (alternating three courses of R-CHOP and R-DHAP followed by the high-dose cytarabine-containing myeloablative regimen that included radiotherapy and melphalan followed by ASCT).

Key Results

Following induction chemotherapy, the overall response rate was high in both arms: 90% for controls and 94% for the cytarabine-containing arm. Complete remission and unconfirmed complete remission rates were higher in the experimental arm: 26% vs 39% (P = .012) and 41% vs 60%, respectively (P = .0003). The percentage of patients able to undergo transplant was similar in both arms (97% for both), and complete remission rates after ASCT were comparable: 63% vs 65%, respectively.

At a median follow-up of 27 months, the experimental arm was superior for the primary endpoint of time to treatment failure: 49 months vs not yet reached (P = .038) due to fewer relapses in the experimental arm (20% vs 10%).

Both arms had comparable safety, with the exception of increased grade 3/4 hematologic toxicity, more renal toxicity, and more patients reporting grade 1/2 nausea in the experimental arm. Toxicities for both myeloablative conditioning regimens were similar, but there was more grade 3/4 mucositis with the high-dose cytarabine regimen and more liver toxicity and constipation in the control arm. ■

References

1. Hermine O, Hoster E, Walewski J, et al: Alternating courses of 3× CHOP and 3× DHAP plus rituximab followed by a high-dose ARA-C containing myeloablative regimen and autologous stem cell transplantation is superior to 6 courses CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma. 52nd ASH Annual Meeting. Abstract 110. Presented December 5, 2010.