American Society of Hematology: Alemtuzumab (Campath) or Standard Treatment with Chlorambucil (Leukeran)
Presenter: Peter Hillmen, MD, Consulting Hematologist, Leeds General Infirmary, Leeds, United Kingdom
In another trial reported by Dr. Hillmen, both response rates and overall survival rates were superior in patients with B-cell chronic lymphocytic leukemia (B-CLL) who received alemtuzumab (Campath, Berlex) instead of the standard treatment (Leukeran medication, GlaxoSmithKline).
In the phase 3, randomized, open-label CAM307 trial, 297 patients (mean age, 59.5 years) with progressive B-CLL in Rai stages I to IV were assigned to receive first-line alemtuzumab (30 mg IV three times per week for 12 weeks) or oral chlorambucil (40 mg/m2 one time for 28 days for 12 cycles or less). The primary endpoint was progression-free survival.
Alemtuzumab was significantly favored in terms of overall response rates—83% for patients receiving alemtuzumab and 55% for those receiving chlorambucil—and in complete response (CR) rates—24% for those receiving alemtuzumab and 2% for those receiving chlorambucil (P < 0.0001).
After a median follow-up period of approximately 25 months, progression-free survival favored the alemtuzumab group (hazard ratio, 0.58; P = 0.0001), as did the time to an alternative treatment (23.3 months for alemtuzumab and 14.7 months for chlorambucil; P = 0.0001). The treatment-free interval was more than double in the alemtuzumab group.
Compared with 0% of patients in the chlorambucil arm, 26% of those in the alemtuzumab arm with CRs achieved minimal residual disease.
Most non-hematological ADEs were infusion-related for alemtuzumab, consisting of fever, chills, nausea, and urticaria. Nausea and vomiting were the most common ADEs associated with chlorambucil.
Grade 3 and 4 hematological toxicities were similar between the groups for anemia and thrombocytopenia, but neutropenia was more common in the alemtuzumab arm (46%) than in the chlorambucil group (28%) (P = 0.0002). Infections, however— not including cytomegalovirus (CMV) events—occurred at a similar rate: in 46% of patients receiving alemtuzumab and in 50% of those receiving canadian chlorambucil.
CMV positivity with symptoms was reported in 23 alem-tuzumab patients (16%). All of these patients recovered without sequelae; 22 had received antiviral agents.
Of the 21 patients who experienced interruptions from therapy with the study drug, 17 resumed treatment after resolution of the infection, and they achieved overall response and CR rates comparable to those of the rest of the population.
“Alemtuzumab therapy was manageable and predictable with no treatment-related deaths,” Dr. Hillmen said.
He emphasized that alemtuzumab is currently given via subcutaneous injections, which are much better tolerated than the intravenous infusions that were used in the CAM307 trial.
He added, “This allow us to consider this treatment as a front-line therapy in poor-risk CLL and in consolidation after chemotherapy where it may have its principal role.”