Obinutuzumab Plus Bendamustine Treatment Active, Adequately-Tolerated Among Patients With R/R CLL

Results from the Phase 2 GABRIELL Trial

According to the phase 2 GABRIELL trial, the combination of obinutuzumab plus bendamustine demonstrated encouraging activity and was adequately tolerated among patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). 

A total of 72 patients with R/R CLL were enrolled in this trial and received the treatment combination for up to 6 cycles of 28 days each. The study end points included overall response rate, progression-free survival (PFS), overall survival (OS), measurable residual disease, and safety. 

Results indicated that the overall response rate was 78.6%, with a median progression-free survival of 26 months. The overall survival had not been reached by the conclusion of the 36-month follow-up period. The researchers assessed that undetectable measurable residual disease of less than or equal to 0.01% (36.4% in bone marrow and 53.4% in peripheral blood, respectively) correlated with a significantly longer PFS and OS than undetectable MRD of greater than or equal to 0.01%.

Among the adverse events reported, neutropenia (58.3%), thrombocytopenia (26.4%), and febrile neutropenia (11.1%) were the most common grade ≥3 events. 

For potential predictive and prognostic factors observed, TP53 disruptions were the sole independent predictive factor for response to the combination treatment (hazard ratio [HR], 0.228). This suggests that TP53 status may be a determinant of treatment efficacy among patients with R/R CLL. Additionally, an unmutated immunoglobulin heavy chain variable region (HR, 16.061) was identified as a negative prognostic factor for PFS. 

Julio Bravo, MD, Hospital Universitario Puerta de Hierro, Madrid, Spain, and coauthors concluded, “The combination of obinutuzumab plus bendamustine is an active and generally adequately-tolerated treatment for R/R CLL.” 

Source: 

Bravo J, Baltasar Tello P, González Garcia E, et al. Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: the phase II GABRIELL study. Leuk Lymphoma. 2023;64(5):913-926. doi:10.1080/10428194.2023.2216327