BENDAMUSTINE (B), FOLLOWED BY OBINUTUZUMAB (G) AND VENETOCLAX (A) IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): CLL2-BAG TRIAL OF THE GERMAN CLL STUDY GROUP (GCLLSG)

Introduction: The prospective, open-label, multicenter phase-II CLL2-BAG trial is based on the theoretical “sequential triple-T” concept [Hallek M., Blood 2013; 122(23): 3723-34] of a tailored and targeted treatment aiming for total eradication of minimal residual disease (MRD). It investigates a sequential treatment with a bendamustine (B) debulking, followed by obinutuzumab (G) and venetoclax (A) as induction and maintenance therapy in an all-comer population of physically fit and unfit, treatment-naïve (TN) and relapsed/refractory (R/R) CLL pts. Methods: Pts with an absolute lymphocyte count ≥25.000/μl and/or lymph nodes ≥5 cm received 2 cycles of B as debulking (70 mg/m2 d1&2 q28 days), unless contraindicated. In the induction G (1000 mg) was administered 3 times in cycle 1 (days 1/2, 8 & 15) and every 4 weeks in cycles 2-6. A was added in cycle 2 with a dose ramp-up (to 400 mg daily) over 5 weeks and several safety precautions. In the maintenance therapy, daily intake of A was continued and G administered every 3 months until achievement of a MRD-negative complete response or for up to 24 months. The primary endpoint is the overall response rate (ORR) at the end of induction therapy; secondary endpoints include MRD evaluations, safety and survival parameters. This primary endpoint analysis is based on uncleaned data, the final analysis will be presented at the meeting. Conclusion: This sequential treatment of B debulking, followed by G and A was very efficacious with an ORR of 97% and a MRD negativity rate of 89% in pB at the end of induction phase. No unexpected toxicities and no clinical TLS were reported. Keywords: ABT-199; chronic lymphocytic leukemia (CLL); obinutuzumab.