CAMPATH IS TOO TOXIC FOR CONSOLIDATION THERAPY OF CLL

NEW YORK (Reuters Health) Aug 16 - The Cancer and Leukemia Group B will no longer test alemtuzumab consolidation after induction therapy in treatment-naive patients with chronic lymphocytic leukemia (CLL).

The group is abandoning this approach because while it improved complete response rates and reduced minimal residual disease, it also led to a high risk of fatal infections.

Dr. John C. Byrd of The Ohio State University, Columbus, and colleagues note online in the Journal of Clinical Oncology on August 9th that patients with CLL invariably relapse even with a complete response to induction therapy. "An important clinical question concerns the value of eliminating minimal residual disease (MRD)."

The monoclonal anti-CD52 antibody alemtuzumab (Campath-1H) is approved for CLL, and preliminary studies showed it could eliminate residual disease after different induction therapies. The team studied the effect of consolidation therapy with alemtuzumab given 3 months after induction therapy with fludarabine and rituximab in 102 patients with CLL, with the hope that the 3-month interval would reduce toxicity.

After induction, the complete response rate was 29% and the partial response rate was 61%, for an overall response rate of 90%. The MRD-negative rate was 15%.

Fifty-eight patients received alemtuzumab. In this group, after alemtuzumab the overall response rate was 91%, the complete response rate increased to 66%, and 50% of the patients were MRD-negative.

However, five patients who had a complete response to induction therapy and received alemtuzumab consolidation died of infectious diseases, the first one 7 months after completing alemtuzumab therapy.

Furthermore, 2-year progression-free survival and overall survival were similar for patients who did and did not receive alemtuzumab.

"Given the toxicity and absence of clear survival benefit, CALGB will not pursue additional studies of alemtuzumab consolidation," the authors state. They do point out that other novel therapeutic agents "are active in CLL and warrant clinical study as potential CLL consolidation therapies."

J Clin Oncol. Posted online August 9, 2010. Abstract