Background and objectives: Autologous stem cell transplantation (ASCT) is effective in mantle cell lymphoma (MCL). We investigated whether incorporation of rituximab into the high-dose regimen might further improve the results of ASCT in patients with MCL.
Design and methods: In a prospective phase II study, patients with newly diagnosed MCL were treated with a sequential dose-escalating therapy comprising standard chemotherapy for remission induction, intensive ara-C-containing chemotherapy for mobilization of stem cells, and myeloablative therapy followed by ASCT. The myeloablative regimen consisted of total body irradiation and high-dose cyclophosphamide supplemented with two doses (375 mg/m3) of rituximab. Outcome parameters (toxicity, clinical and molecular response as assessed by allele-specific IGH real-time quantitative polymerase chain reaction (RQ-PCR), event-free survival, and overall survival) were compared with those of 34 historical controls treated identically but without rituximab.
Results: Thirty-four patients were accrued. Whereas engraftment, toxicity and clinical response were not different from those in controls, event-free survival was significantly increased with rituximab (not reached vs. 43 months; hazard ratio 0.38; p=0.036). This was associated with a trend for a superior molecular response rate in 11 study vs. 10 control patients with a marker available (73% vs. 30%, p=0.086) despite similar levels of lymphoma contamination of the stem cell inocula infused.
Interpretation and conclusions: Incorporation of two standard doses of rituximab into the myeloablative regimen might improve outcome of up front ASCT for MCL, allowing long-term disease control to an extent previously not reached in this disease.