Phase III Trial Shows Venetoclax/Obinutuzumab Active in First-Line Treatment of CLL
Posted: Monday, October 7, 2019
Obinutuzumab combined with venetoclax offered patients longer progression-free survival than did obinutuzumab with chlorambucil, in a cohort of previously untreated patients with chronic lymphocytic leukemia (CLL) who have coexisting conditions. Almost 80% of patients in the experimental arm completed fixed-duration treatment with the combination of the monoclonal antibody and the BCL2 inhibitor, the authors reported in The New England Journal of Medicine, demonstrating the safety profile of the regimen. However, they noted, longer follow-up is needed to determine the durability of responses.
The 432 participants (median age, 72 years; median Cumulative Illness Rating Scale score, 8) in the open-label, randomized phase III trial were evenly divided between the venetoclax and chlorambucil arms, reported Kirsten Fischer, MD, of University Hospital Cologne and University of Cologne in Germany, and colleagues. “After a median follow-up of 28.1 months, 30 primary endpoint events (disease progression or death) had occurred in the venetoclax plus obinutuzumab group and 77 had occurred in the chlorambucil plus obinutuzumab group (P < .001),” they wrote. At 24 months, the progression-free survival rate was 88.2% in the venetoclax arm versus 64.1% in the chlorambucil arm.
In contrast to a previous trial’s findings, venetoclax plus obinutuzumab was not associated with a higher frequency of tumor-lysis syndrome, pointed out Dr. Fischer and her co-investigators, which they attributed, at least in part, to the trial’s safety measures. Additionally, the differences between the venetoclax and chlorambucil groups in terms of the incidence of grade 3 or 4 neutropenia, grade 3 or 4 infections, and all-cause mortality were not statistically significant.
The authors suggested that the fixed-duration venetoclax/obinutuzumab regimen warrants comparison with continuous ibrutinib monotherapy. “Recent data indicate that up to 41% of patients discontinue treatment with ibrutinib after a median of 7 months,” wrote the researchers.
Disclosure: The study authors’ disclosure information may be found at nejm.org.
