Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia in the Western hemisphere, accounting for between 25% and 35% of all leukemias in the United States. According to the American Cancer Society, nearly 24,000 new cases of CLL will be diagnosed in the United States this year, and about 4,500 individuals will die from the disease.
The current standard of care for patients with CLL includes indefinite treatment with a Bruton’s tyrosine kinase (BTK) inhibitor—such as ibrutinib, acalabrutinib, or zanubrutinib—which may result in long-term toxicities, like atrial fibrillation, bleeding, and hypertension. In addition, patients often develop drug resistance, leading to disease relapse or progression.
The results from a phase Ib dose-escalation/expansion study of the investigational human monoclonal antibody ianalumab (VAY736) in combination with ibrutinib in patients with CLL show that the therapy was well tolerated and allowed some patients to discontinue ibrutinib and remain off therapy for 12 to 24 months. The study by Rogers et al is published in Clinical Cancer Research.
Study Methodology
The researchers enrolled 39 patients with CLL (n = 15 in the escalation arm, n = 24 in the expansion arm) who had not experienced a complete remission on ibrutinib or had developed resistance mutations. Participants received intravenous ianalumab every 2 weeks and continued ibrutinib once daily for up to eight cycles of 28 days. The study evaluated the safety, tolerability, recommended dose, and antitumor activity of this drug combination.
Results
No dose-limiting toxicities were observed. Of the 39 participants in the study, 38.5% achieved complete remission or complete remission with incomplete marrow recovery at cycle 9 (C9). At C9 day 1, 17 patients (43.6%) achieved undetectable measurable residual disease in the blood or bone marrow. Grade ≥ 3 adverse events occurred in 16 patients (41.0%) and were treatment-related in 9 (23.1%).
No on-treatment deaths were reported; one patient died of COVID-19 infection during the posttreatment period. Seventeen patients (43.6%) discontinued ibrutinib at or after C9 day 1 and remained off therapy for 12.1 to 24.5 months.
Preliminary RNA sequencing and flow cytometry data support both NK- and T-cell activation with ianalumab.
“The combination was well tolerated, with 43.6% of patients discontinuing ibrutinib therapy. Biomarker data suggest that ianalumab increased NK- and T-cell activation. These data support further evaluations of ianalumab in combination with Bruton tyrosine kinase inhibitors for patients with CLL,” concluded the study authors.
Reducing the Burden of Cancer on Patients
The results from this study have important implications for patients with CLL, according to senior author John C. Byrd, MD, Director of the UPMC Hillman Cancer Center and Associate Vice Chancellor for Cancer Affairs at the University of Pittsburgh School of Medicine.
“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,” he explained. “These results point to potentially using fixed-duration combination therapy to achieve remission and reduce the burden of continuous treatment.”
Kerry A. Rogers, MD, of the Division of Hematology, Department of Internal Medicine at The Ohio State University, is the corresponding author of this study.
Disclosure: Funding for this study was provided by Novartis Pharmaceuticals Corporation. For full disclosures of the study authors, visit aacrjournals.org/clincancerres.
