A recent study published in Clinical Cancer Research highlights the potential of a new combination therapy for patients with chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults. Research indicates that adding the investigational antibody ianalumab (VAY736) to the existing treatment with ibrutinib (Imbruvica) may allow some patients to discontinue daily medication, thereby improving their overall quality of life.
Approximately 200,000 individuals in the United States are affected by CLL. This treatment approach aims to address the challenges associated with long-term use of ibrutinib, which, while effective, can lead to long-lasting toxicity and psychological burdens. According to John C. Byrd, MD, the study’s senior author and director of the UPMC Hillman Cancer Center, “BTKis have revolutionized CLL treatment, but patients typically stay on them indefinitely.”
The study involved a Phase I, open-label, multicenter trial that enrolled 39 patients who either 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 trial primarily focused on safety, tolerability, and the potential for the combination therapy to deepen responses, allowing patients to stop taking ibrutinib.
Byrd and his team found that the combination therapy was well-tolerated, with no dose-limiting toxicities reported. While 41% of patients experienced grade 3 or greater adverse events, primarily involving low levels of neutrophils, the overall response rate was nearly 60%. In addition, 43.6% of participants achieved undetectable measurable residual disease (uMRD) in their blood or bone marrow.
The results revealed that 17 patients were able to stop taking ibrutinib and remained off therapy for periods ranging from 12 to 24 months. The biomarker analyses suggested that ianalumab enhanced the activation of natural killer (NK) and T-cells, supporting its mechanism of action in combating CLL.
“Patients who experience deep responses can stop daily medication, a powerful shift that removes the constant reminder of cancer,” Byrd explained. He emphasized that the psychological impact of taking daily medication can be significant for individuals with blood cancers.
The findings from this study carry important implications for the treatment of CLL. The combination therapy may help patients avoid the cumulative toxic effects associated with lifelong BTK inhibitor therapy. Notably, infection rates among trial participants were lower than those typically reported with single-agent BTK inhibitor therapy, indicating that the addition of ianalumab did not increase the risk of infection.
“These results point to the potential for using fixed-duration combination therapy to achieve remission and reduce the burden of continuous treatment,” Byrd stated.
Despite these promising results, the study’s limitations include a small sample size and a lack of long-term follow-up data. Byrd called for larger trials to confirm whether this approach could become a standard strategy for reducing the duration of BTK inhibitor treatment.
The findings are a significant step forward in the ongoing quest to improve the lives of those affected by chronic lymphocytic leukemia, offering hope for a future where patients may not have to rely on continuous medication. For further details, refer to the study 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 appear in Clinical Cancer Research in 2025.
