Favorable outcomes with venetoclax plus obinutuzumab (VenG) continued during long-term follow-up compared with venetoclax plus chlorambucil (ClbG) among patients with treatment-naive chronic lymphocytic leukemia (CLL) with comorbidities, according to an updated analysis of the CLL14 trial presented at the ASCO20 Virtual Scientific Program.
The CLL14 trial previously demonstrated an improvement in progression-free survival (PFS) with VenG compared with ClbG among patients with previously untreated patients with CLL and comorbidities. This updated analysis provides longer-term outcomes with a median follow-up of 39.6 months.
The CLL14 trial randomly assigned 432 patients with treatment-naive CLL with comorbidities to receive VenG or ClbG. The primary endpoint was investigator-assessed PFS and secondary endpoints included response rates, minimal residual disease (MRD), and overall survival (OS). All patients are off study treatment and follow-up is ongoing.
The superior PFS with VenG compared with ClbG was maintained with longer follow-up, with a 3-year PFS of 81.9% with VenG compared with 49.5% with ClbG. Median PFS was not reached in the VenG arm and was 36 months in the ClbG arm (hazard ratio [HR], 0.31; 95% CI, 0.22-0.44; P <.001).
The PFS benefit was consistent among patients with a TP53 mutation or deletion and among patients with mutated or unmutated IGHV.
“This is particularly interesting, as in the earlier follow-up, no PFS difference had been observed between both treatment arms in patients with mutated IGHV status,” Othman Al-Sawaf, MD, of the University of Cologne in Germany, and lead author and presenter of the poster, said. “However, now with the longer follow-up, it becomes clear that venetoclax-obinutuzumab also yields higher efficacy for patients with mutated IGHV status.”
The rate of MRD was also higher in the VenG arm, with 47.2% having undetectable MRD in peripheral blood (defined as <10-4) compared with 7.4% in the ClbG arm.
Median OS was not yet reached, but there was no significant difference between arms in this analysis (HR, 1.03; 95% CI, 0.60-1.75; P =.92).
There were no new safety signals reported. In the VenG arm, 17% of patients developed new second primary malignancies compared with 10.3% in the ClbG arm.
These data suggest that VenG maintained superior efficacy during long-term follow-up, Dr Al-Sawaf said. “Of note, these benefits were observed across all known risk categories, indicating that this regimen is a viable option for patients with previously untreated CLL.”
Al-Sawaf O, Zhang C, Tandon M, et al. Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: Follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(15_suppl):abstr 8027.