Addition of Obinutuzumab or Rituximab to Chlorambucil in Treatment-Naive Patients with CLL: Updated Survival Analysis from the CLL11 Study
Obinutuzumab (GA101) is a glycoengineered anti-CD20 monoclonal antibody that is being evaluated in patients with chronic lymphocytic leukemia (CLL) with comorbidities. The 3-arm randomized CLL11 study compared obinutuzumab plus chlorambucil versus rituximab plus chlorambucil and chlorambucil alone in 781 treatment-naïve patients with CLL.1 At a preplanned analysis, the study results showed statistically significant superiority of obinutuzumab/chlorambucil compared with chlorambucil in terms of progression-free survival (PFS) and overall survival (OS); obinutuzumab/chlorambucil also showed superiority compared with rituximab/chlorambucil in terms of PFS but not for OS. Goede and colleagues reported updated results on survival and time to next treatment (TTNT) at this meeting.2
Enrolled patients had a median age of 73 years and a median cumulative Illness Rating Scale total score of 8 . At a median follow-up time of 42.4 months, obinutuzumab/chlorambucil therapy resulted in significant improvements in efficacy outcomes, including PFS (median PFS, 31.1 vs 11.1 months; hazard ratio [HR], 0.20; P <.0001), TTNT (median TTNT: 51.1 vs 15.1 months; HR, 0.24; P <.0001), and OS (median OS: not reached vs 58.5 months; HR, 0.62; P = .0167) compared with chlorambucil. In comparison to rituximab/chlorambucil, obinutuzumab/ chlorambucil treatment showed superiority in terms of PFS (median PFS: 28.7 vs. 15.7 months; HR; 0.46; P <.0001) and TTNT (median TTNT: 51.1 vs 38.2 months; HR, 0.57; P <.0001). Although a trend for OS benefit with obinutuzumab/chlorambucil treatment continued to be seen, it did not reach statistical significance (HR, 0.77; P = .0932). The trend for OS benefit with obinutuzumab/chlorambucil treatment extended to most patient subgroups. Overall, the authors concluded that the updated results of the CLL11 study confirmed the previous results in terms of significant improvements in PFS, TTNT, and OS benefit with obinutuzumab/chlorambucil compared with chlorambucil alone, and clinically meaningful PFS and TTNT benefits compared with rituximab/chlorambucil.
- Goede V, et al. N Engl J Med. 2014;370:1101-1110.
- Goede V, et al. ASH 2015. Abstract 1733.