5.56 Ofatumumab in Combination with High-Dose Methylprednisolone as a Salvage Treatment for Heavily Pretreated or Refractory Patients with Chronic Lymphocytic Leukemia

Abstract

Treatment options for relapsed / refractory or heavily pretreated patients with chronic lymphocytic leukemia (CLL) are limited, and these patients typically have a poor prognosis. We conducted a study to evaluate the combination of High-dose methylprednisolone (HDMP) with ofatumumab (HDMP-O) in patients who were not considered eligible to receive chemotherapy due to the presence of comorbidities, poor performance status, severe cytopenias and / or refractory status to fludarabine or alemtuzumab. Patients received HDMP 1 g/m2 IV daily × 3 every 28 days for three consecutive cycles, and ofatumumab 300 mg (dose 1) followed by 11 doses of 2,000 mg over a 6 month period, along with prophylactic antimicrobial therapy (trimethoprim-sulfamethoxazole 160/800 mg twice a day × 3 per week, fluconazole 100 mg/day and valganciclovir 900 mg/day). Eight patients were evaluated; all of them were males with progressive and symptomatic CLL. Median age was 69 years (range 49–78 years). The mean number of prior treatment regimens was 3.75, including four patients that had previously received HDMP and rituximab and two patients that underwent matched unrelated donor stem cell transplantation. All patients had been previously treated with rituximab, 75% of the patients were refractory to fludarabine and / or aletuzumab, and 88% had high-risk disease based on the presence of unfavorable cytogenetics (17p-, 11q-), unmutated IgVH status, or ZAP-70 expression. Bulky disease and splenomegaly were present in 62.5% of patients. All patients completed the planned therapy with no major side effects or toxicities. There was no evidence of myelosupression, and even patients with pancytopenia improved their peripheral blood counts. Response assessment based on the IW-CLL 2008 criteria showed an overall response rate of 50% (4 partial responses), 25% of patients had stable disease and the remainder showed progressive disease. The median time to progression in responders was 7 months. Overall survival 6 months after treatment was 65%. This study suggests that the combination of HDMP and Ofatumumab is a safe and effective salvage regimen for high-risk CLL patients who otherwise would not be candidates for additional treatment.