Ibrutinib Combination Therapies for Patients With CLL

A recent study examining the scientific rationale and clinical results of ibrutinib combinations in chronic lymphocytic leukemia (CLL) found that the combination of ibrutinib and targeted agent venetoclax may provide high complete response rates and, importantly, high rates of undetectable minimal residual disease (MRD; Blood Cancer J. 2021;11[4]:79. doi:10.1038/s41408-021-00467-7.).

Low complete remission rates, development of resistance, and uncommon substantial toxicities are some of the limitations of Ibrutinib as a treatment for CLL. Because Ibrutinib must be used until disease progression, it creates a financial burden on patients with CLL. “These limitations were the impetus for the development of ibrutinib combinations” wrote Natalia Timofeeva, Pre-clinical Cancer Researcher, University of Texas MD Anderson Cancer Center, and colleagues.

This study reviewed the rationale and clinical outcomes of combinations of ibrutinib with immunotherapy, chemoimmunotherapy, cell therapy, and other targeted therapy. Among these strategies, ibrutinib combined with targeted agent venetoclax resulted in high complete response and high rates of undetectable MRD.

These results allow for testing fixed-duration therapy and an MRD-guided approach to discontinuation of treatment for patients with CLL. Time-limited therapy is more cost-effective than continuous regimens used until disease progression.

“More selective BTK inhibitors, such as acalabrutinib, tirabrutinib, and zanubrutinib, are being tested in similar combinations. Further, the use of combination strategies to target different elements of the pathophysiology of CLL at an early stage may result in lower rates of emergence of drug-resistant clones” concluded Dr Timofeeva and colleagues, adding “Long-term results will provide this long-needed information.”—Marta Rybczynski