Ofatumumab is safe and effective as front-line treatment in older patients with chronic lymphocytic leukemia and severe co-morbidities, including other malignancies

Abstract Background The majority of patients with chronic lymphocytic leukemia (CLL) are older and have multiple comorbidities, including other cancer diagnoses. These patients are routinely excluded from participation in clinical trials. Objective In this phase II study, we determined the activity and toxicity of ofatumumab, a fully human anti-CD20 monoclonal antibody, in older patients with CLL, poor performance status and comorbidities. Methods Treatment-naive patients with CLL aged ≥65 years with an ECOG performance status of 2–3 or Charlson comorbidity index ≥2 were eligible. Ofatumumab was administered intravenously weekly for the first month, then monthly for a total of 12 months. Results Thirty-four patients were enrolled. Median age was 73 years, and 29% had another cancer diagnosis. Among 32 patients evaluable for response, the overall response rate was 72%. We observed complete responses in 19% of patients and partial responses in 53%. The median progression-free survival duration was 21 months, and the estimated proportion of patients alive at 36 months was 87%. All 34 patients were evaluable for toxicity. Treatment was well tolerated, with infusion-related reactions being the most common treatment-related adverse event. Only one patient had a grade 3 infection. Additional grade 3 adverse events that may have been related to ofatumumab were diarrhea, nausea/vomiting, hyperglycemia, pulmonary embolism, and hypersensitivity reaction, each in one patient. No grade 4 adverse events were observed. Conclusion Single-agent ofatumumab is a well-tolerated and effective therapeutic approach for treatment-naive older patients with CLL; it can be safely administered to patients with significant comorbidities and other cancer diagnoses.