Compared with chlorambucil plus obinutuzumab, venetoclax plus obinutuzumab appears to yield good responses for a limited duration among patients with previously untreated chronic lymphocytic leukemia (CLL), according to research published in The Lancet Oncology.

The treatment of elderly or unfit patients with CLL is difficult, and it is critical to balance therapy efficacy with tolerability. While chlorambucil plus obinutuzumab is a frequently used chemoimmunotherapy regimen in this setting, some novel therapies, including the Bruton tyrosine kinase inhibitor, ibrutinib, have shown promise in recent studies. Despite improvement in efficacy, there is concern that because some novel therapies require consistent use until disease progression, adverse events and patient inability to afford medication may preclude their use.

The randomized, phase 3 CCL14 trial (ClinicalTrials.gov Identifier: NCT02242942)  previously found that fixed-duration venetoclax, a potent and selective inhibitor of B-cell lymphoma-2 (BCL-2), may be effective when used with obinutuzumab for CLL treatment. In their report, study authors followed up with eligible participants who had not received treatment for at least 24 months.

From August 2015 to 2016, 432 patients with CLL were enrolled and assigned to either the venetoclax plus obinutuzumab (216 patients) group or a chlorambucil plus obinutuzumab (216 patients) group. At baseline, characteristics were balanced between the 2 groups. The median ages in the venetoclax and chlorambucil groups were 72 years and 71 years, respectively; 68% vs 66% of patients were men, the median time since diagnosis was 31.2 months vs 29.2 months, and B-symptoms were present in 48% and 52% of patients in the venetoclax and chlorambucil groups, respectively.


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At time of data collection, all patients had been off treatment for at least 2 years; the median follow-up period was 39.6 months. Patients in the venetoclax group had longer progression-free survival compared with the chlorambucil group (not reached vs 35.6 months, respectively; hazard ratio, 0.31; P <.0001). In the venetoclax vs chlorambucil groups, 4% vs 26% of patients had high minimal residual disease (MRD) status, respectively, 5% vs 22% had low MRD, and 76% vs 35% had undetectable MRD.

Neutropenia was the most common grade 3 or 4 adverse event and occurred at a similar rate in both groups (53% in the venetoclax group vs 48% in the chlorambucil group). Overall, in the venetoclax group, grade 3, 4, and 5 events occurred at frequencies of 35%, 35%, and 9%, respectively; and at frequencies of 41%, 31%, and 5%, respectively, in the chlorambucil group. One (1%) treatment-related death was noted in the venetoclax group compared with 2 (1%) treatment-related deaths in the chlorambucil group.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21(9):1188-1200. doi:10.1016/S1470-2045(20)30443-5