Ofatumumab As Initial Therapy For Indolent B Cell Lymphomas: A Phase Ii Trial

Abstract Background Single agent monoclonal antibodies (mAb) such as rituximab are an attractive treatment option for patients with low grade B-cell lymphoma given proven efficacy and tolerability. Ofatumumab offers potential advantages over rituximab including increased affinity for the CD20 antigen, increased complement dependent cytotoxicity, and is fully humanized which may predict a lower incidence of infusion reactions. We therefore investigated ofatumumab\as initial therapy for indolent B-cell lymphomas. Methods We conducted a phase II trial of ofatmumab monotherapy. Eligible patients were adults with previously untreated indolent B-cell lymphomas including follicular lymphoma grade 1-2, marginal zone lymphoma and small lymphocytic lymphoma. Subjects had to have measurable disease >2cm and not be candidates for potentially curative radiotherapy for localized disease. Ofatumumab was administered as 8 weekly infusions at a flat dose of 1000 mg. The primary end point was complete response rate (CRR) as defined by the International Workshop Response Criteria (1999). Restaging CT scans were performed 4 weeks after the final dose of study drug. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and toxicity. The study was designed with 90% power to show a 50% CRR, with a 30% CRR considered unworthy of further study. Results Between March 2011 and December 2012, 42 eligible subjects were enrolled (28 follicular lymphomas, 4 marginal zone lymphomas, and 10 small lymphocytic lymphomas). With 41 of 42 subjects completing all 8 infusions, the CRR was 9.5% with a PRR of 42.9% (ORR of 52%). The median PFS has not been reached at a median follow-up of 9 months. The 12 month PFS was 86% (95% CI [72%, 99%]). One patient died due to progressive disease. There were 22 (52%) grade 1-2 and 7 (17%) grade 3 infusion reactions despite standard pre-medications including acetaminophen, hydrocortisone, and diphenhydramine. There were no cases of grade 3-4 neutropenia. Conclusion Ofatumumab did not appear to improve the CRR compared to what would be expected from rituximab in patients with previously untreated indolent B-cell lymphomas. Incidence of infusion reactions was significant with this fully humanized mAb. Disclosures: Off Label Use: Ofatumumab is an anti-CD20 monoclonal antibody approved for the treatment of relapsed chronic lymphomcytic leukemia that is refractory to fludarabine and alemtuzumab.