CAM307 is a phase III, open-label, multinational, randomized controlled trial comparing alemtuzumab (CAM) with chlorambucil (CHLO) for previously untreated BCLL requiring therapy. Eligible patients with Rai Stages I–IV were randomized 1:1 to either CAM 30 mg IV tiw for up to 12 weeks or CHLO 40 mg/m2 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 ≥200 cells/μL. The primary endpoint was PFS; secondary endpoints were response rate, overall survival, and safety. A total of 297 patients were enrolled (CAM n=149 and CHLO n=148); median age: 60 years; performance status 0–1: 96%; maximum lymph node size ≥5 cm: 22%; and Rai Stage I–II: 63%, Rai Stage III–IV: 33%. Diagnosis, Rai Stage, response and disease progression were confirmed by an independent response review panel (IRRP). CAM has a significantly prolonged PFS compared to CHLO (p=0.0001; see KM survival curve).PFS in CAM vs CHLO patients with adverse cytogenetic findings of del 17p (n=21) was 10.7 mo vs 2.2 mo and for trisomy 12 (n=39) was 18.3 mo vs 12.9 mo. Results were similar for patients with del 11q (n=54, 8.5 mo vs 8.6 mo). Common (≥15%) CAM reported adverse events (AEs) (n=147), likely infusion-related, included pyrexia (70%), chills (53%), nausea (18%), hypotension (16%) and urticaria (16%). Common AEs (≥15%) in the CHLO arm (n=147) were nausea (37%) and vomiting (18%). Frequency of asymptomatic CMV viremia on the CAM arm was 52%; CMV infection occurred in only 16%, none grade 4. CAM treatment was interrupted in 56% of CMV viremic patients, and resumed in 92% with ORR 92% (31% CR). Ganciclovir was administered to 41% of CAM patients with CMV viremia. Infections, including CMV, were reported in 76% of CAM and 50% of CHLO patients while on study. Relevant grade 3/4 treatment-emergent events included (CAM vs CHLO): lymphopenia (97% vs 3%), pyrexia (8% vs 0%), CMV events (8% vs 0%) and chills (3% vs 0%). Treatment emergent grade 3/4 thrombocytopenia (16% vs 13%) and anemia (14% vs 19%) were similar, and although grade 3/4 neutropenia was more common with CAM, (45% vs. 26%), AEs of CAM vs CHLO bacteremia/sepsis (3% vs 2%) and febrile neutropenia (5% vs 3%) were comparable. Serious AEs were reported for 44% of CAM (20% for IV Ganciclovir only in CMV viremic patients) and 20% of CHLO patients while on study treatment. CONCLUSIONS: CAM307 demonstrates that therapy-naïve BCLL patients treated with CAM have significantly longer PFS and higher ORR than those treated with CHLO, with manageable toxicities. Although CMV reactivation was reported in the CAM arm, prompt intervention maintained efficacy. The activity seen here supports ongoing investigations of CAM in first line combination therapy, high risk patients and consolidation.
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Disclosures: SIRARD - Medical Director at Genzyme Corporation.; HILLMEN - Schering AG/Genzyme Corporation.; Sirard - stock options and employee stock purchase plan at Genzyme Corporation.; Robak/Skotnicki - with Genzyme Corporation; Hillmen - with Schering AG.; Jaksic - from Genzyme Corporation.; Hillmen - Speakers Bureau for Schering AG/Genzyme Corporation.
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