Alemtuzumab (Campath), a CDR-grafted monoclonal antibody, recognizes the CD52 antigen which is expressed on normal B and T cells as well as on leukemic B-cell chronic lymphocytic leukemia (B-CLL) cells. Alemtuzumab(Drug information on alemtuzumab) induced a clinical response in 33% of fludarabine-refractory CLL patients (Blood 94[suppl 1]:705a, 1999), and also in eight of nine previously untreated patients (Br J Haematol 93:151, 1996).
We present here the final analysis of a phase II study evaluating the clinical effects of subcutaneous, long-term (18-week) administration of alemtuzumab (dosage escalated rapidly from 3 mg to 10 mg to 30 mg three times per week) to 41 previously untreated CLL patients requiring therapy. Prophylactic treatment with acyclovir, trimethoprim(Drug information on trimethoprim) and sulfamethoxazole(Drug information on sulfamethoxazole), and fluconazole(Drug information on fluconazole) (Diflucan) was administered.
The overall response rate was 87% in the 38 evaluable patients who had received at least 2 weeks of therapy (intent-to-treat group: 81% overall response). 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]). Complete response in the bone marrow required 18 weeks of therapy in most patients. Lymphadenopathy responded to treatment in 87% of the patients. The median time to 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 site reactions (NCI grade 1/2) occurred during the first 1 to 2 weeks of therapy in most patients. Transient grade 4 neutropenia was recorded in 24% of the patients. Four patients had cytomegalovirus reactivation (causing fever without pneumonitis and promptly responding to intravenous ganciclovir(Drug information on ganciclovir) (Cytovene). In two of these patients, alemtuzumab was restarted without recurrence of cytomegalovirus. One patient (who was allergic to trimethoprim and sulfamethoxazole) had a Pneumocystis carinii pneumonia infection.
CONCLUSION: Alemtuzumab is a highly active agent in patients with previously untreated CLL. Prolonged administration seems to be important in order to achieve high-quality remissions, especially in the bone marrow. The subcutaneous route was well tolerated and may be recommended not only for alemtuzumab, but also for many other monoclonal antibodies, with benefits such as reduced cost and self-administration.