Phase II trial of R‐CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601. (22nd October 2015)

• Record Type: Journal Article
• Authors: Till, Brian G.; Li, Hongli; Bernstein, Steven H.; Fisher, Richard I.; Burack, W. Richard; Rimsza, Lisa M.; Floyd, Justin D.; DaSilva, Marco A.; Moore, Dennis F.; Pozdnyakova, Olga; Smith, Sonali M.; LeBlanc, Michael; Friedberg, Jonathan W.
• Is Part Of: British journal of haematology. Volume 172:Number 2(2016)
• Page Start: 208
• Page End: 218
• Publication Date: 2015-10-22
• Subjects: lymphoma -- chemotherapy -- mantle cell lymphoma -- maintenance therapy -- proteasome inhibition; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13818
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: 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/m 2 days 1 and 4 of 21 d cycles) followed by bortezomib maintenance (1·3 mg/m 2 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.