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: W. G. Wierda, T. Kipps, J. Mayer, S. Stilgenbauer, T. Robak, C. D. Williams, R. Furman, G. Chan, C. Russell, A. Österborg
Journal: Journal of Clinical Oncology (2009)

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 (&gt;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. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .