Long-Term Evaluation of Efficacy and Safety of Ofatumumab Added to Fludarabine & Cyclophosphamide in Subjects with Relapsed Chronic Lymphocytic Leukemia: Final Analysis of Complement 2 Trial

Introduction: COMPLEMENT 2 is a phase III, randomized, open-label study, which compared the efficacy of ofatumumab (OFA) in combination with fludarabine and cyclophosphamide (FC) vs FC therapy alone in patients (pts) with relapsed chronic lymphocytic leukemia (CLL). In a previous interim analysis (2015) performed based on 194 progression-free survival (PFS) events, OFA+FC showed significant improvement of PFS and was well tolerated compared to FC in pts with relapsed CLL. Here, we report the 5-year follow-up of overall survival (OS) and safety profile of the drugs evaluated in this study. Methods: Based on stratification factors (number of prior CLL therapies and Binet stage), pts with relapsed CLL were randomized 1:1 to Arm A (OFA+FC) and Arm B (FC alone). Arm A received OFA intravenously (IV) (300 mg on day 1, cycle [c] 1; 1000 mg on day 8, c1; and 1000 mg on day 1, c2-6) in addition to FC (F [IV]: 25 mg/m2 and C [IV]: 250 mg/m2 on days 1-3, c1-6). Arm B received FC only. Pts who had achieved a complete response or partial response following at least 1 prior CLL therapy, but whose disease had progressed after >6 months (mo) were included in the present study. The primary endpoint was PFS. Key secondary endpoints were OS, time to next treatment (TTNT), and safety. During the primary analysis for PFS, all the type 1 error (1-sided alpha 0.025) was spent, resulting in no alpha remaining for inferential interpretation of the final analysis for OS. The final analysis results will be used for descriptive and supportive purposes only. Results: A total of 365 pts were randomly assigned to receive OFA+FC (n=183) or FC (n=182) in the final analysis. Overall, 119 (65%) and 102 (56%) pts completed the scheduled OFA+FC and FC treatments, respectively. Adverse events (AEs) were the main reason for treatment discontinuation in both treatment arms (50 [27%] pts in the OFA+FC arm and 52 [29%] in the FC arm). A total of 332 (91%) pts entered the follow-up phase, 172 (94%) from the OFA+FC arm and 160 (88%) from the FC arm. The follow-up phase for the OFA+FC and FC arms was approximately 41 mo and 23 mo, respectively. Baseline characteristics were similar in both arms. Median PFS was not assessed for the final analysis because the final results for the primary endpoint of PFS were reported as part of the primary analysis. PFS was 28.9 mo for OFA+FC and 18.8 mo for FC (hazard ratio [HR]=0.67, 95% confidence interval [CI]: 0.51, 0.88; p=0.0032). The final OS analysis was perf