Phase II trial of R- CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601.

Bortezomib is active in mantle cell lymphoma ( MCL), with approval in upfront and relapsed settings. Given inevitable recurrence following induction chemoimmunotherapy, maintenance approaches are a rational strategy to improve clinical outcomes. We conducted a phase II study to evaluate the safety and efficacy of six cycles of R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus bortezomib (1·3 mg/m2 days 1 and 4 of 21 d cycles) followed by bortezomib maintenance (1·3 mg/m2 days 1, 4, 8, and 11 every 3 months for 2 years). Sixty-five eligible patients were enrolled. The treatment was well tolerated and toxicities were mainly haematological. The rate of grade ≥3 peripheral neuropathy was low (5%). With a median follow-up of 6·8 years, 2-year progression-free survival ( PFS) was 62%, and 2-year overall survival ( OS) was 85%. At 5 years, PFS was 28% and OS was 66%. MCL International Prognostic Index scores were significantly associated with 2-year PFS, but did not predict long-term (≥5-year) PFS. Baseline Ki-67 index was significantly associated with survival. Combination R- CHOP with bortezomib followed by maintenance bortezomib appears to improve outcomes compared historically with R- CHOP alone, with prolonged remissions in a subset of patients. These results suggest that inclusion of bortezomib with induction chemotherapy and/or maintenance is promising in MCL and warrants further exploration. [ABSTRACT FROM AUTHOR]