Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia: A phase 2 study.

This phase 2 study describes long-term clinical and immunological effects of fixed-duration ofatumumab (anti-CD20) and alemtuzumab (anti-CD52) combination immunotherapy in 52 patients with previously untreated CLL. The median age was 65 years (range 45-79), 60% had Rai stage 3-4, 40% were IgHV unmutated and 25% had del(17p)/TP53 mutation. Alemtuzumab was given subcutaneously (30 mg tiw, 18 weeks) and ofatumumab intravenously (300-2000 mg) starting week 3 q2 weeks (8 doses). Overall response rate was 98% with 48% complete remissions including 60% bone marrow MRD-undetectable. After a median follow-up time of 68 months, the median PFS, TTNT, DOR and OS were 31, 62, 30 months and not reached, respectively. The estimated 5-year PFS, TTNT, DOR and OS were 35%, 51%, 35% and 87%, respectively. CD59 (complement-inhibitory molecule) was rapidly downregulated (p < 0.01) during the initial CD52 mAb run-in period. Our study demonstrated that dual targeting of CD20 and CD52 represents an early successful example of time-limited (4-5 months) chemotherapy-free precision therapy for previously untreated CLL.