Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a Phase 4, non--interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia

We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. The total number of patients was 103, with a median age of 65 years (range, 39-85). The median number of prior lines of therapy was 4 (range, 1-13), including in most cases rituximab-, fludarabine- and alemtuzumab- based regimens; thirteen patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. The study herein reported is registered as ClinicalTrial.gov National Cancer Institute 01453062.