Phase II Study of Subcutaneous Alemtuzumab (Campath) Therapy in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Alemtuzumab (Campath), a CDR-grafted monoclonal antibody, recognizes the CD52antigen which is expressed on normal B and T cells as well as on leukemic B-cellchronic lymphocytic leukemia(B-CLL) cells. Alemtuzumab induced a clinical response in 33% offludarabine-refractory CLL patients (Blood 94[suppl 1]:705a, 1999), and also ineight of nine previously untreated patients (Br J Haematol 93:151, 1996).

We present here the final analysis of a phase II study evaluating theclinical effects of subcutaneous, long-term (18-week) administration ofalemtuzumab (dosage escalated rapidly from 3 mg to 10 mg to 30 mg three timesper week) to 41 previously untreated CLL patients requiring therapy.Prophylactic treatment with acyclovir, trimethoprim and sulfamethoxazole, andfluconazole (Diflucan) was administered.

The overall response rate was 87% in the 38 evaluable patients who hadreceived at least 2 weeks of therapy (intent-to-treat group: 81% overallresponse). Ninety-five percent had a complete response (CR) in the blood and 79%responded in the bone marrow (45% CR plus 34% partial response [PR]). Completeresponse in the bone marrow required 18 weeks of therapy in most patients.Lymphadenopathy responded to treatment in 87% of the patients. The median timeto treatment failure has not yet been reached (18+ months).

Most patients had transient National Cancer Institute (NCI) grade 1/2 fever,but very few other first-dose reactions were observed. Local injection sitereactions (NCI grade 1/2) occurred during the first 1 to 2 weeks of therapy inmost patients. Transient grade 4 neutropenia was recorded in 24% of thepatients. Four patients had cytomegalovirus reactivation (causing fever withoutpneumonitis and promptly responding to intravenous ganciclovir (Cytovene). Intwo of these patients, alemtuzumab was restarted without recurrence ofcytomegalovirus. One patient (who was allergic to trimethoprim andsulfamethoxazole) had a Pneumocystis carinii pneumonia infection.

CONCLUSION: Alemtuzumab is a highly active agent in patients with previouslyuntreated CLL. Prolonged administration seems to be important in order toachieve high-quality remissions, especially in the bone marrow. The subcutaneousroute was well tolerated and may be recommended not only for alemtuzumab, butalso for many other monoclonal antibodies, with benefits such as reduced costand self-administration.

Click here to read Dr. Bruce Cheson's commentary on this abstract.