Treatment with fixed-duration venetoclax and obinutuzumab is more effective and results in deeper remissions than chlorambucil and obinutuzumab for patients with previously untreated chronic lymphocytic leukemia (CLL), according to follow-up data presented during the ASCO20 Virtual Scientific Program.
In the previous phase 3 CLL14 trial (ClinicalTrials.gov Identifier: NCT02242942), investigators evaluated outcomes in patients with CLL and found that fixed-duration venetoclax-obinutuzumab demonstrated superior progression-free survival (PFS) compared with chlorambucil-obinutuzumab. In this open-label analysis, investigators conducted a follow-up to assess efficacy and safety of treatment in previously untreated patients with CLL.
The primary outcome was investigator-assessed PFS. Secondary outcomes included response rates, rates of minimal residual disease, and overall survival (OS). Although follow-up analysis is currently still in progress, all patients have been off study treatment for at least 24 months.
A total of 432 patients were included in the analysis and randomly assigned (1:1) to received either 12 cycles of venetoclax or obinutuzumab with 6 cycles of obinutuzumab (216 patients per group).
After a median follow-up of 39.6 months, PFS was continuously better among patients treated with venetoclax-obinutuzumab compared with chlorambucil-obinutuzumab (hazard ratio [HR], 0.31; P <.001). After 3 years, the estimated PFS rate was 81.9% for venetoclax-obinutuzumab and 49.5% for chlorambucil-obinutuzumab. Even among patients with mutated or deleted TP53 and unmutated immunoglobulin heavy chain variable region gene, PFS was still significantly longer for participants of the venetoclax-obinutuzumab arm.
Eighteen months after treatment, minimal residual disease was undetectable in 47.2% of patients treated with venetoclax-obinutuzumab and 7.4% of patients treated with chlorambucil-obinutuzumab. OS rates were not significantly different for either group (HR, 1.027; P =.921), and median OS was not reached in either group.
In addition, secondary primary malignancies were reported in 17% and 10.3% of participants of the venetoclax-obinutuzumab and chlorambucil-obinutuzumab groups, respectively.
“The results suggest that the superior efficacy and deep remissions after fixed-duration [venetoclax-obinutuzumab] are maintained during extended follow-up, and show the long-term benefits of 12 cycles of [venetoclax-obinutuzumab] across all known categories,” the authors concluded.
Disclosure: This study was supported by F. Hoffman-La Roche and AbbVie. See original article for authors’ full disclosures.
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(suppl):abstr 8027.
This article originally appeared on Hematology Advisor