Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic Lymphocytic Leukemia

Abstract

Patients and MethodsPatients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period (dose 1 ϭ 300 mg; doses 2 to 12 ϭ 2,000 mg); response by an independent review committee (1996 National Cancer Institute Working Group criteria) was assessed every 4 weeks until week 24 and then every 3 months until month 24. Results This planned interim analysis included 138 treated patients with FA-ref (n ϭ 59) and BF-ref (n ϭ 79)CLL. The overall response rates (primary end point) were 58% and 47% in the FA-ref and BF-ref groups, respectively. Complete resolution of constitutional symptoms and improved performance status occurred in 57% and 48% of patients, respectively. Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group, respectively, and 5.9 and 15.4 months in the BF-ref group, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. Hematologic events during treatment included anemia and neutropenia. ConclusionOfatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.

Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies

“…Thus, an interim analysis in an international phase I trial of ofatumumab, used as single agent at a dose of 2000 mg in refractory CLL patients, reported a good safety profile and a high overall response rate in heavily pretreated patients. 40 A multicenter phase I study of GA-101, used as single agent at escalating doses of 400-2000 mg, showed good responses with two cases of complete remission at intermediate doses (800/1200 mg), a tumor-burden decrease and good tolerance in 11/13 evaluable CLL patients. 41 Finally, an ongoing phase I study is testing LFB-R603 at doses escalating from 75 to 1650 mg/m 2 .…”

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

“…The humanized anti-CD20 antibody ofatumumab was recently approved for the treatment of fludarabine-and alemtuzumab-refractory patients, resulting in 58% OR and a median PFS of 5.7 months. However, this antibody showed little benefit in fludarabine-refractory patients harboring the 17p deletion and bulky lymphadenopathy (OR 14%) [8]. Therapy with HDMP, with or without anti-CD20 antibody rituximab, was shown to be effective in refractory CLL [9][10][11], including cases with the TP53 mutation, with reported OR of 69% and median PFS of 12 months [12].…”

Refractory chronic lymphocytic leukemia - new therapeutic strategies

“…Like in the dose-escalating study cited above, the most common adverse events were infusion reactions and infectious complications. Efficacy was lower in CLL with 17p deletion [19].…”