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 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 and sulfamethoxazole, and
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 (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