Subcutaneous Administration of Alemtuzumab: A Single Institution Experience.

Abstract

Alemtuzumab is an active drug in the treatment of a number of lymphoid malignancies and is currently indicated for intravenous administration to patients with B-cell chronic lymphocytic leukemia (CLL) who have failed therapy with fludarabine. Unfortunately, despite premedication, grade 3/4 infusion-related reactions (IRR) are common during alemtuzumab IV administration (fever = 19%, rigors = 16%, and hypotension = 5%, amongst others). If grades 1/2 IRR are included, these numbers increase to 86%, 85%, and 32%, respectively. Nausea also occurs in 54% of patients. In addition to complicating therapy, these reactions sometimes make it necessary to prematurely discontinue therapy. These toxicities may be avoided by administering alemtuzumab subcutaneously (SC); a promising modality, but one with limited supporting data. We report the results of our institutional experience with SC alemtuzumab administration. We performed a retrospective chart review examining data points related to demographics, safety, and efficacy. This IRB - approved review looked at 20 patients who were treated with SC alemtuzumab (13 = CLL, 1 = CLL/AML, 3 = CTCL, 3= PTCL); 2 of these were retreated subcutaneously after receiving IV therapy. Treatment was attempted with a dose-escalation scheme of 3mg-10mg-30mg; with the goal of a 12-week regimen. The average age of the patients was 61 (median 62, range 45–76). 13 were male and 7 were female. The average number of weeks of subcutaneous therapy received was 7 (median 7, range 1–12 weeks). The average number of prior treatment regimens was 3 (median 2, range 1–7). ORR to therapy with alemtuzumab= 60%. (CR = 4, PR = 8). 9 patients had refractory or progressive disease. Patients tolerated the therapy well. Toxicities were all grades 1/2 and usually resolved with supportive therapy and continued alemtuzumab administration; these included hemolytic anemia (n=1), mild pruritis (n=1), anemia (n=1), neutropenia (n=2), fever (n=3), rigors (n=2) mild skin reactions (n=2). Infectious complications included bacterial pneumonia (n=1), herpes zoster (3 months after the completion of therapy, n=1), CMV reactivation (antiviral therapy with alemtuzumab held for two weeks, n=1). No patients discontinued therapy due to grade 3/4 IRR. Of particular interest are the two patients retreated with SC alemtuzumab after previously receiving the drug IV. (1 = PR after first and second course, 1 = PR after first course and no response to second course.) These patients tolerated the drug well with minimal toxicity. One of the retreated patients who had experienced bronchospasm with IV therapy, had no respiratory issues with subcutaneous administration. Based on this data, we conclude that SC alemtuzumab is a safe, well-tolerated, and effective alternative to IV administration. Final data will be available at presentation.