Results of a phase II multicenter study of obinutuzumab plus bendamustine in pts with previously untreated chronic lymphocytic leukemia

Background: Bendamustine (B) plus rituximab (R; BR) is a commonly used first-line (1L) treatment for chronic lymphocytic leukemia (CLL). The CLL10 study reported an overall response rate (ORR) of 96%and complete response (CR) rate of 31%with BR. Obinutuzumab (GA101; G) is a glycoengineered, type II anti CD20 monoclonal antibody. A randomized Phase III trial in 1L CLL pts showed that G significantly improved progression-free survival (PFS) and CR rate compared with R, when used in combination with chlorambucil (Goede 2014). B plus G (BG) was evaluated in a subgroup of CLL pts in the GREEN study (Stilgenbauer 2015). Aims: The aim of this Phase II study (NCT02320487) is to evaluate the efficacy and safety of BG as 1L treatment for CLL pts. Methods: 102 pts with previously untreated CLL received BG, consisting of 6 cycles of G (cycle [C] 1: 100mg day (D) 1, 900mg D2, 1000mg D8 and D15; C2-6: 1000mg D1) and B (90mg/m2: C1, D2 and D3; C2-6, D1 and D2). Each cycle was 28 days. The primary endpoint was CR assessed using iwCLL criteria. Secondary endpoints included ORR, PFS, overall survival, and minimal residual disease (MRD). Median follow-up at the time of analysis was 11.0 months. Results: Median pt age was 61 yrs (range 35-90); 68.6%were male; 44.1%had Rai stage 3-4. For evaluated pts, IgVH status was 32.9%mutated and 67.1%unmutated. The incidences of trisomy 12, normal cytogenetics, and deletions of 13q, 11q, and 17p were 23.4%, 37.5%, 17.2%, 15.6%, and 6.3%, respectively. Investigator-assessed CR rate was 49.0%(95%CI 39.0-59.1) and ORR was 89.2%(95%CI 81.5-94.5) after 6 cycles. MRD negativity in blood, as measured by 4-color flow cytometry, was achieved in 42.7%of pts at the end of induction response assessment and in 75.5%of pts at any time following treatment. MRD negativity in bone marrow (BM) was 60.8%in pts with BM samples. The most common adverse events (all grades [Gr]) were infusion reactions (72.5%), nausea (52.0%), pyrexia (36.3%), neutropenia (34.3%), fatigue (34.3%), constipation (26.5%), and rash (26.5%). The most common Gr 3-4 adverse event was neutropenia (26.5%). Incidence of Gr 3-4 infections was 11.8%. Incidence of tumor lysis syndrome was 4.9%(all Gr 3). Three pts died; none were deemed related to study treatment or CLL by investigators. Summary/Conclusions: BG is an effective regimen for 1L treatment of CLL pts, inducing a high CR rate after 6 cycles of therapy. No unexpected safety signals were observed.