Ofatumumab, a Novel CD20 Monoclonal Antibody, Is Active in Patients With Fludarabine- and Alemtuzumab-Refractory or Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia Irrespective of Prior Rituximab

Brief Abstract Ofatumumab, a novel CD20 monoclonal antibody, produces high response rates regardless of prior rituximab exposure in patients with fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia. Full Abstract Background Patients with CLL refractory to fludarabine and alemtuzumab (FA-ref) or refractory to fludarabine with bulky (> 5 cm) lymphadenopathy (BF-ref) have poor outcomes with current salvage therapy (overall response rate [ORR], 23%; overall survival [OS], 9 months). Ofatumumab is a human monoclonal antibody that binds a distinct membrane-proximal epitope on the CD20 molecule and elicits more efficient in vitro complement-dependent cytotoxicity of B-cell lines and primary tumor cells versus rituximab. We assessed whether prior rituximab exposure impacted outcomes with ofatumumab in patients with FA-ref or BF-ref CLL enrolled in an international, pivotal trial. Patients and Methods Patients received 8 weekly ofatumumab infusions followed by 4 monthly infusions (infusion, 1300 mg; infusions 2–12, 2000 mg). The primary endpoint was ORR (1996 NCI-WG criteria) assessed by an Independent Endpoint Review Committee over 24 weeks. Secondary efficacy endpoints included progression-free survival (PFS) and OS. Results In the 59 FA-ref and 79 BF-ref patients at the planned interim analysis, ORR was 58% (95% CI, 40%–74%) and 47% (95% CI, 32%-62%), respectively. Median PFS was 5.7 months (95% CI, 4.5–8.0 months) and 5.9 months (95% CI, 4.9–6.4 months), and median OS was 13.7 months (95% CI, 9.4-[not yet reached] months) and 15.4 months (95% CI, 10.2-20.2 months), respectively. In the subgroup of FA-ref (n = 35) and BF-ref (n = 43) patients who previously received a rituximab-containing regimen, ORR was 54% and 44%, and median PFS was 5.5 months (95% CI, 3.7–8.0 months) and 5.5 months (95% CI, 3.8–6.4 months), respectively. In FA-ref and BF-ref patients refractory to fludarabine in combination with rituximab and cyclophosphamide (n = 16 in each group), ORR was 50% and 44%, and median PFS was 4.6 months (95% CI, 2.3–6.4 months) and 5.6 months (95% CI, 2.1–6.6 months), respectively. Conclusion Single-agent ofatumumab is active in patients with FA-ref and BF-ref CLL, irrespective of prior anti-CD20 monoclonal antibody therapy with rituximab, including refractoriness to fludarabine-based regimens containing rituximab.