engleski

Progression free survival is superior with alemtuzumab vs chlorambucil as front-line therapy for patients with B-cell chronic lymphocytic leukemia

Background. CAM307 is a phase III, open-label, multinational, randomized controlled trial comparing alemtuzumab (CAM) to chlorambucil (CHLO) for previously untreated BCLL. Aims.To compare efficacy and safety of alemtuzumab (CAM) to chlorambucil (CHLO) as front-line therapy. Methods. Eligible patients had Rai Stage I-IV and were randomized 1:1 to either CAM 30 mg IV tiw up to 12 weeks or CHLO 40 mg/m po q 28 days up to 12 cycles. CAM patients received prophylactic trimethoprim/sulfamethoxazole DS and famciclovir treatment during therapy and until CD4 counts were less than 200 cells/L. The primary endpoint was PFS ; secondary endpoints included response rate, time to alternative therapy, survival, and safety. A total of 297 patients were randomized (CAM n=149 and CHLO n=148 ; median age: 60 years) ; performance status 0-1: 96% ; maximum lymph node size less than 5 cm: 22% ; and Rai stage I-II: 63%. An independent response review panel (IRRP) confirmed diagnosis, Rai stage, response and disease progression that were used in the efficacy analysis. Results. PFS was superior for CAM (p=0.0001, stratified log-rank test) with a hazard ratio of 0.58 (95%CI: 0.43, 0.77). Response rate was higher for CAM than CHLO, previously reported (ASH, 2006 ; 301). CAM was superior to CHLO in patients <65 years of age, <70 years of age, with maximum lymph node size <5 cm, and performance status <2 as measured by PFS and response rates. Kaplan-Meier median time to alternative treatment was significantly longer for CAM (23.3 months) compared to CHLO (14.7 months) ; p=0.0001 (stratified log-rank test), hazard ratio 0.54 (95%CI: 0.39, 0.74). With a median duration on treatment of 11.7 weeks for CAM and 28.3 weeks for CHLO, the difference in time off active treatment is even greater for the CAM patients. There was no overall difference in overall survival with 24 deaths in each arm and a median follow-up time of 2 yrs for the study. A trend towards improved PFS with CAM was observed in patients with 17p deletion, not statistically significant due to small sample size. Common drug related adverse events (AEs) (≥15%) in the CAM arm (n=147) were pyrexia (64%), CMV PCR positivity (53%), chills (50%) and urticaria (15%) and in the CHLO arm (n=147) were nausea (35%) and vomiting (18%). Symptomatic CMV infection occurred in 16% in CAM arm only, none grade 4. Excluding CMV, infections occurred in 46% of CAM and 50% of CHLO patients. Relevant grade 3/4 treatment-emergent AEs (CAM vs CHLO): pyrexia (8% vs 0%), CMV events (8% vs 0%) and chills (3% vs 0%). Treatment-emergent grade 3/4 thrombocytopenia (12% vs 12%) and anemia (11% vs 18%) were similar for CAM vs CHLO. Although grade 3/4 treatment emergent neutropenia was more common with CAM vs CHLO (41% vs 25%), bacteremia/sepsis (3% vs 2%) and febrile neutropenia (5% vs 3%) were comparable. Conclusions. CAM307 demonstrates that CAM is superior when compared to CHLO in therapy-naive BCLL patients with significantly longer PFS, time to alternative treatment, higher overall ORR, CR and MRD negative rate, with manageable toxicities.

CLL; alemtuzumab; chlorambucil

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