ORLANDOIn first-line therapy of chronic lymphocytic leukemia (CLL), alemtuzumab(Drug information on alemtuzumab) (Campath) has superior efficacy to the standard treatment, oral chlorambucil(Drug information on chlorambucil), with manageable toxicity, according to results of the CAM307 trial. Peter Hillmen, MD, consultant hematologist at Leeds General Infirmary, Leeds, UK, presented the results at the American Society of Hematology 48th Annual Meeting (abstract 301).
CAM307 is a phase III randomized open-label study of 297 patients (mean age, 59.5 years) with progressive Rai stage I-IV CLL. The trial was requested by the US FDA at the time of alemtuzumab's initial approval in 2001 with an indication of relapsed and refractory CLL. Patients were randomized to alemtuzumab 30 mg IV three times a week for 12 weeks or oral chlorambucil 40 mg/m2 once daily for 28 days for up to 12 cycles.
The overall response rate (83% alemtuzumab, 55% chlorambucil) and complete response rate (alemtuzumab 24%, chlorambucil 2%) both significantly favored alemtuzumab (P < .0001). After a median follow-up of approximately 25 months, progression-free survival (PFS) favored the alemtuzumab group (HR 0.58, P = .0001), as did time to alternative treatment (23.3 months alemtuzumab, 14.7 months chlorambucil, P = .0001). The treatment-free interval was more than double in the alemtuzumab group (see Table).
Furthermore, in the alemtuzumab arm, 26% of the complete response patients achieved minimal residual disease negativity, compared with 0% in the chlorambucil arm.
Stratifying results according to cytogenetic abnormality, Dr. Hillmen said that significant alemtuzumab advantages were seen among patients with 11p deletions and 13q (as sole deletion), with a strong favoring trend for 17p deletions. PFS significantly favored alemtuzumab-treated patients with the 13q deletion.
The most common adverse events in the chlorambucil group (excluding infections) were fever, chills, nausea, and urticaria, Dr. Hillmen said, and in the alemtuzumab group, nausea and vomiting. Most adverse events were infusion related. While grade 3-4 hematologic toxicities were similar between groups for anemia and thrombocytopenia, neutropenia was more common in the alemtuzumab arm (46% vs 28%, P = .0002).