Chronic lymphocytic leukemia (CLL), the most common form of adult leukemia in the Western Hemisphere, affects approximately 200,000 individuals in the United States alone. A recent study published in Clinical Cancer Research suggests that the combination of the investigational antibody ianalumab (VAY736) with ibrutinib (Imbruvica) may allow some patients to discontinue daily therapy, potentially enhancing their quality of life.
The study explored how ianalumab, which targets the B-cell activating factor receptor (BAFR), interacts with ibrutinib, a member of the Bruton’s tyrosine kinase inhibitors (BTKi) class. According to John C. Byrd, MD, the senior author and chair of the Department of Internal Medicine at the University of Cincinnati College of Medicine, BTKis have transformed CLL treatment, but patients often remain on them indefinitely, which can lead to long-term toxicity. Byrd emphasized that daily treatment can serve as a constant reminder of illness, creating psychological burdens for patients.
In collaboration with his team, including Kerry A. Rogers, MD, from The Ohio State University, Byrd tested this innovative treatment approach to help patients avoid extended therapy. Preclinical studies from Byrd’s lab indicated that ianalumab demonstrated enhanced activity when combined with BTKi drugs against CLL.
The Phase I trial involved 39 patients who had not achieved complete remission on ibrutinib or had developed resistance mutations. Participants received intravenous ianalumab every two weeks along with a standard dose of ibrutinib for up to eight cycles. The study focused on evaluating safety, tolerability, and antitumor activity, as well as the potential to deepen responses enough for patients to discontinue BTKi therapy.
Byrd reported that the combination therapy did not result in dose-limiting toxicities. While 41% of patients experienced grade 3 or greater adverse events, primarily low levels of neutrophils, the overall response rate was nearly 60%. Notably, 43.6% of participants had undetectable measurable residual disease (uMRD) in their blood or bone marrow.
Seventeen patients successfully stopped their ibrutinib therapy and remained off treatment for periods ranging from 12 to 24 months. Biomarker analyses revealed that ianalumab enhanced the activation of natural killer (NK) and T-cells, supporting its proposed mechanism of action. Byrd highlighted that thirteen patients achieved uMRD in both blood and bone, and four patients had uMRD only in bone, indicating deep responses.
“Patients who experience deep responses can stop daily medication, a powerful shift that removes the constant reminder of cancer,” Byrd explained. He added, “Taking a medicine every day can be a reminder of sickness for patients, so it is very symbolic for patients with blood cancers to be able to go off therapy.”
The findings from this study have significant implications for CLL patients, suggesting that this approach could help them avoid the cumulative toxicity associated with lifelong BTKi therapy. Infection rates among trial participants were lower than those historically reported with single-agent BTKi therapy, indicating that the addition of ianalumab did not increase the risk of infection.
Byrd concluded, “These results point to the potential for using fixed-duration combination therapy to achieve remission and reduce the burden of continuous treatment.” However, he acknowledged the study’s limitations, including its small sample size and lack of long-term follow-up. He called for larger trials to confirm whether this approach could become a standard strategy for reducing the duration of BTKi treatment.
Further details on this research can be found in the article titled “Investigating the addition of ianalumab (VAY736) to ibrutinib in patients with chronic lymphocytic leukemia (CLL) on ibrutinib therapy: results from a phase Ib study,” set to be published in Clinical Cancer Research in 2025.
