A recent study has revealed promising results for chronic lymphocytic leukemia (CLL) patients, suggesting that a combination treatment may allow some individuals to discontinue daily use of the medication ibrutinib. The findings, which will be published in Clinical Cancer Research in 2025, indicate that the investigational antibody ianalumab (VAY736) could enhance the effectiveness of ibrutinib, a widely used therapy for CLL.
According to the research led by John C. Byrd, MD, from the UPMC Hillman Cancer Center, the combination therapy could significantly improve the quality of life for patients. CLL, the most common form of leukemia among adults in the Western Hemisphere, affects around 200,000 individuals in the United States alone. Traditional treatment with ibrutinib often requires lifelong commitment, which can lead to long-term toxicity and psychological burdens for patients.
Byrd, who is also the director of the UPMC Hillman Cancer Center and an associate vice chancellor for cancer affairs at the University of Pittsburgh School of Medicine, emphasized the importance of this study. “BTK inhibitors have revolutionized CLL treatment, but patients typically stay on them indefinitely and the therapy can cause long-term toxicity,” he stated.
The research team, including Kerry A. Rogers, MD, from The Ohio State University, conducted a Phase I, open-label, multicenter trial that enrolled 39 patients who were either not in complete remission on ibrutinib or had developed resistance mutations. These participants received intravenous doses of ianalumab every two weeks alongside ibrutinib for up to eight cycles, aiming to evaluate the treatment’s safety, tolerability, and antitumor activity.
The results were encouraging, with an overall response rate of nearly 60%. Notably, 43.6% of participants achieved undetectable measurable residual disease (uMRD) in their blood or bone marrow. Byrd highlighted that 17 patients successfully discontinued ibrutinib and remained off therapy for between 12 and 24 months.
The mechanism of action for ianalumab involves blocking signals from the B-cell activating factor receptor (BAFR), which prevents the survival and maturation of cancerous B cells. This action also marks these cells for destruction by the immune system’s natural killer (NK) cells. “Patients who experience deep responses can stop daily medication, a powerful shift that removes the constant reminder of cancer,” Byrd remarked.
Additionally, the research indicated that the infection rates among trial participants were lower than those historically associated with single-agent BTK inhibitor therapy, suggesting that the combination did not increase the risk of infections. Byrd noted, “These results point to potentially using fixed-duration combination therapy to achieve remission and reduce the burden of continuous treatment.”
Despite the promising findings, Byrd acknowledged limitations, including the small sample size and the need for long-term follow-up. He stated, “A larger trial is needed to confirm whether this approach can become a standard strategy for reducing BTKi treatment duration.” The study represents a significant step forward in the treatment of CLL, potentially offering patients a path to a better quality of life while reducing the long-term impact of their disease.