Lay Summary: Combining two antibodies against CLL is being explored
Rituximab, an anti-CD20 monoclonal antibody, has only recently provoked interest for the treatment of CLL. It is now widely used, both as a single agent and in combination with chemotehrapy. Alemtuzumab is a recombinant, fully humanized, monoclonal antibody against the CD52 antigen. Monotherapy with alemtuzumab has produced response rates of 33% to 53%, with a median duration of response ranging from 8.7 to 15.4 months, in patients with advanced CLL who were previously treated with alkylating agents and had failed or relapsed after second-line fludarabine therapy.25–27 In addition, alemtuzumab has proven effective even in patients with poor prognostic factors, including high-risk genetic markers such as deletions of chromosome 11 or 17 and p53 mutations. It is a toxic drug and is currently used mostly in other than first line settings.
There is only one published phase II trial of the combination of the two drugs. Forty-eight patients were treated and were assessable for response (32 with chronic lymphocytic leukemia [CLL], 9 with CLL/prolymphocytic leukemia [PLL], 1 with PLL, 4 with mantle cell leukemia/lymphoma, 2 with Richter transformation). The overall response rate was 52% (complete remission, 8%; nodular partial response, 4%; partial response, 40%). With a median follow-up of 6.5 months (range, 1-20 months), the median time to progression was 6 months (range, 1-20 months); median survival, 11 months (11+ months for responders vs 6 months for nonresponders). Most toxicities were grade 2 or lower and infusion-related. Infections occurred in 52% of the patients. Cytomegalovirus (CMV) antigenemia assays were positive in 27% of the patients, but only 15% were symptomatic and required therapy. The combination of rituximab and alemtuzumab is feasible, has an acceptable safety profile, and has clinical activity with a short course in a group of patients with poor prognoses.
Michael Hallek, Chronic Lymphocytic Leukemia (CLL): First-Line Treatment Hematology 2005
© 2005 The American Society of Hematology
Rai KR, Freter CE, Mercier RJ, et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002;20:3891–3897.
Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002;99:3554–356
William G. Wierda, Thomas J. Kipps, Michael J. Keating Novel Immune-Based Treatment Strategies for Chronic Lymphocytic Leukemia Journal of Clinical Oncology, Vol 23, No 26 (September 10), 2005: pp. 6325-6332
Faderl S, Thomas DA, O’Brien S et al. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies. Blood 2003;101:3413–3415