Activity of ofatumumab, a novel CD20 mAb, and prior rituximab exposure in patients with fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia (CLL)
Authors: Wierda W. G. , Kipps T. , Mayer J. , Stilgenbauer S. , Robak T. , Williams C. D. , Furman R. , Chan G. , Russell C. , Österborg A. 
Published: August 2020

7044^

Background: Salvage therapy has limited activity (20–26% overall response rate [ORR]) in patients (pts) with CLL refractory to fludarabine and alemtuzumab (double-refractory, DR) or refractory to fludarabine with bulky (>5 cm) lymphadenopathy (bulky fludarabine-refractory, BFR). Ofatumumab (OFA) is a fully human mAb that targets a unique small-loop epitope of CD20 close to the cell surface and elicits more potent in vitro complement-dependent cytotoxicity of B-cell lines and tumor cells vs rituximab (RTX). To determine whether prior RTX exposure impacted activity of OFA in pts with DR or BFR CLL, an analysis was performed to assess efficacy by prior RTX exposure in pts treated with OFA in an international, pivotal study. Methods: Pts with DR or BFR CLL received 8 weekly infusions of OFA followed by 4 monthly infusions (Dose 1, 300 mg; Doses 2–12, 2,000 mg). Primary endpoint was ORR (1996 NCI-WG criteria) assessed by an Independent Review Committee over 24 weeks. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Results: Among 138 treated pts (DR, N=59; BFR, N=79) at the planned interim analysis, the ORR (99% CI) was 58% (40, 74%) in the DR group and 47% (32, 62%) in the BFR group. Median PFS (95% CI) was 5.7 mo (4.5, 8.0) and 5.9 mo (4.9, 6.4), and median OS (95% CI) was 13.7 mo (9.4, NYR) and 15.4 mo (10.2, 20.2), respectively. 59% and 54% of DR and BFR pts, respectively, previously received RTX-containing regimens. Both ORR and median PFS were similar in the prior RTX and no prior RTX subgroups (Table), and were comparable to efficacy data for the overall study population. ORR and median PFS were also similar in pts refractory to fludarabine in combination with RTX with or without cyclophosphamide. Conclusions: Single-agent therapy with OFA is effective in pts with DR or BFR CLL, irrespective of prior CD20 mAb therapy with RTX.

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