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Safety and disease response to MEDI-551, an anti-CD19 antibody, in chronic lymphocytic leukemia patients previously treated with rituximab
© Forero et al; licensee BioMed Central Ltd. 2013
Published: 7 November 2013
The expression of CD19 on chronic lymphocytic leukemia (CLL) cells offers a novel therapy for relapsed CLL patients (pts) previously treated with rituximab. MEDI-551 is an affinity-optimized anti-CD19 Ab with enhanced Ab-dependent cellular cytotoxicity (ADCC) effector function.
Response and toxicity of single-agent MEDI-551 in multiply relapsed CLL pts with prior rituximab therapy was assessed in a phase 1/2 (ph 1/2), open-label, dose-escalation and expansion study. Combination therapy was assessed in an ongoing phase 2 (ph 2) study comparing MEDI-551 or rituximab+bendamustine in relapsed/refractory CLL pts. For the ph 1/2 study, B cell depletion was assessed with flow cytometry and BAFF biomarker analysis; response was assessed using the 2008 IWG criteria.
In the ph 1/2 study, 26 CLL pts received ≥1 dose of MEDI-551. In the ph 2 study, 44 pts received study drug as of 20Mar2013. Loss of CD19 detection due to depletion and/or occupancy with MEDI-551 was rapid and apparent after cycle 1. B cell depletion occurred 1 day after dose 1 and was associated with increased serum BAFF concentrations. In the ph 1/2 study, of 21 MEDI-551-treated CLL pts evaluable for response, 5 achieved partial remission and 13 had stable disease. Commonly reported adverse events (AEs) in MEDI-551 pts were infusion-related reactions (IRRs; 62%), nausea (23%), pyrexia (23%), and neutropenia (23%) in the 26 ph 1/2 pts; in the 29 ph 2 pts, they were nausea (62%), IRRs (31%), pyrexia (28%), chills (28%), and fatigue (28%). 11 pts had ≥ grade 3 AEs in the ph 1/2 study and 16 in the ph 2. Common treatment-related AEs: IRRs (58%) and nausea (12%) in the ph 1/2; nausea (52%), IRRs (28%), chills (24%), and fatigue (24%) in the ph 2. Three treatment-unrelated AEs of general health deterioration (ph 1/2), subarachnoid hemorrhage (ph 1/2), and sepsis (ph 2), resulted in death.
MEDI-551 as a single agent demonstrated B-cell depletion, increased serum BAFF levels, clinical activity, and an acceptable risk-benefit profile in relapsed/refractory CLL pts. Preliminary results of the ongoing ph 2 study of MEDI-551+bendamustine demonstrated an acceptable safety profile.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.