Triplet Therapy May Not Provide Additional Benefit in Older Patients With CLL

Adding Venclexta to Imbruvica and Gazyva did not boost progression-free survival in older patients with chronic lymphocytic leukemia, research showed.

Adding Venclexta (venetoclax) to Imbruvica (ibrutinib) and Gazyva (obinutuzumab) did not provide additional survival benefit compared with Imbruvica and Gazyva in the treatment of older patients with chronic lymphocytic leukemia (CLL), according to findings from a recent phase 3 study.

Results from this study, which focused on patient experiences during the COVID-19 pandemic, were presented at the 2023 American Society of Clinical Oncology Annual Meeting.

“Our study demonstrates that the triple therapy — or adding (Venclexta) to (Imbruvica) and (Gazyva) as a course of treatment for older patients with CLL — is not superior in terms of progression-free survival,” Dr. Jennifer Woyach, co-leader of the by The Ohio State University Comprehensive Cancer Center – James Leukemia Research Program and the study’s lead investigator, said in a press release from her institution.

According to the study abstract, findings from smaller trials have previously demonstrated that triple therapy with Venclexta, Imbruvica and Gazyva can result in undetectable minimal residual disease, which refers to a very small number of cancer cells in the body during or after treatment. Undetectable minimal residual disease may be believed to allow for discontinuation of treatment.

In this study, researchers analyzed data from 465 patients (median age, 74 years) with CLL who were assigned either the triple therapy (233 patients) or treatment with Imbruvica and Gazyva (232 patients).

Researchers focused on progression-free survival, defined as the time from when patients were assigned a treatment until disease progression or all-cause death, which was assessed for up to 10 years, according to the study’s ClinicalTrials.gov listing.

During a median follow-up of 14 months, progression-free survival in patients treated with Imbruvica and Gazyva was 87.5% versus 85% in those who received triple therapy. Events occurred in 29 patients in the double-therapy group (including 23 deaths, four disease progressions and two patients who started other therapy) and in 35 patients from the triple-therapy group (including seven disease progressions and 28 deaths).

Patients were registered into this study between Jan. 4, 2019, and July 15, 2022, which includes time during the COVID-19 pandemic. The leading cause of death in both treatment groups was COVID-19, attributing to 11 deaths in the double-therapy group and 19 deaths in the triple-therapy group, according to the abstract.

“The pandemic had a clear impact on our trial, and long-term follow-up of our patients will be critical to determine the outcome of this triple therapy with special attention to minimal residual disease and therapy discontinuation,” Woyach said in the release.

Other mortality causes were related to 13 deaths in the double-therapy group and 11 deaths in the triple-therapy group.

The rate of side effects considered severe or worse were similar in both groups.

Of note, to be considered for enrollment in the trial, patients had to be diagnosed with intermediate or high-risk CLL or small lymphocytic lymphoma, according to the ClinicalTrials.gov listing. Patients also had to be aged 65 years or older and had to complete treatment with Rituxan (rituximab) and/or high-dose corticosteroids at least four weeks before enrollment.

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