It is unclear whether adding venetoclax to treatment with ibrutinib and obinutuzumab can improve outcomes in older patients with treatment-naïve chronic lymphocytic leukemia (CLL), according to a presentation at the ASCO Annual Meeting 2023.

Results from the phase 3 trial showed that adding venetoclax to ibrutinib and obinutuzumab did not improve progression-free survival (PFS). However, this result may have been influenced by an imbalance of COVID-19 deaths between the treatment arms, according to study presenter Jennifer Ann Woyach, MD, of The Ohio State University Comprehensive Cancer Center in Columbus.

The trial (ClinicalTrials.gov Identifier: NCT03737981) included 465 patients with previously untreated CLL who were 65 years of age or younger. The patients were randomly assigned to receive ibrutinib and obinutuzumab (IO; n=232) or venetoclax plus ibrutinib and obinutuzumab (IVO; n=233). Baseline characteristics were well balanced between the arms.


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The rate of grade 3-5 hematologic adverse events was 48% in the IO arm and 61% in the IVO arm (P =.006). The rate of grade 3-5 non-hematologic adverse events was 66% and 67%, respectively (P =.743).

Grade 3 or higher COVID-19 was reported in 16 patients in the IO arm and 31 in the IVO arm. COVID-19 was fatal in 11 patients in the IO arm and 19 of those in the IVO arm.

At 18 months, the PFS rate was 87% in the IO arm and 85% in the IVO arm (hazard ratio [HR], 1.12; 95% CI, 0.70-1.79). When COVID-19 deaths were censored, the PFS rate was 92% in the IO arm and 94% in the IVO arm (HR, 0.82; 95% CI, 0.44-1.53).

At 18 months, the overall survival (OS) rate was 90% in the IO arm and 87% in the IVO arm (HR, 1.34; 95% CI, 0.80-2.25; P =.26). When COVID-19 deaths were censored, the OS rate was 95% in the IO arm and 96% in the IVO arm (HR, 0.97; 95% CI, 0.46-2.04; P =.93).

The complete response rate was 31.3% in the IO arm and 68.5% in the IVO arm. The rate of minimal residual disease negativity was 33.3% and 86.8%, respectively.

“In this trial, IVO is not superior to IO for the initial treatment of older patients with CLL,” Dr Woyach said. “However, COVID-19 may have significantly altered these results, with data suggesting a death imbalance for patients treated with IVO as compared with IO.”

Dr Woyach said long-term follow-up will be “critical” to determine if some patients benefit from IVO.  

Disclosures: This research was partly supported by Pharmacyclics, AbbVie, Genentech, and Abbott Molecular. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Woyach JA, Yin J, Brown JR, et al. Results of a phase 3 study of IVO vs IO for previously untreated older patients (pts) with chronic lymphocytic leukemia (CLL) and impact of COVID-19 (Alliance). ASCO 2023. June 2-6, 2023. Abstract 7500.