Dr Islam on the Limited Use of Ibrutinib in CLL

Prioty Islam, MD, MSc, attending physician, medical oncologist, Leukemia, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, discusses the current status of the first-generation BTK inhibitor ibrutinib (Imbruvica) following the FDA approvals of next-generation BTK inhibitors in patients with chronic lymphocytic leukemia (CLL) and expands on the few instances in the clinic where she may lean toward treatment with ibrutinib instead of the next-generation BTK inhibitors zanubrutinib (Brukinsa) or acalabrutinib (Calquence).

Islam details that she rarely sees patients with CLL whose disease profiles are best suited for ibrutinib in place of acalabrutinib or zanubritinib. However, she occasionally sees these patients in her practice, she amends, adding that for certain patient subsets, ibrutinib is the only BTK inhibitor with published safety or efficacy data.

A phase 2 trial (NCT02420912) being led out of the University of Texas MD Anderson Cancer Center is evaluating ibrutinib in 1 of these patient subsets, Islam says. This trial is investigating the use of ibrutinib with nivolumab (Opdivo) in the treatment of patients with relapsed/refractory or high-risk untreated CLL, small lymphocytic lymphoma, or Richter transformation. Findings from this trial indicate that ibrutinib in combination with nivolumab can be an effective treatment approach for patients whose disease displays Richter transformation, Islam expands. Notably, this regimen addresses an unmet need for patients with Richter transformation, as there is a limited amount of safe and effective treatment options for this population. In patients with Richter transformation, Islam says she would not trial a next-generation BTK inhibitor because there are no data to support the use of those agents in that population.

Based on the data from that phase 2 trial and the continued development of next-generation BTK inhibitors, ibrutinib should only be used in subsets of patients with CLL in whom no safety or efficacy data with other agents are available, Islam emphasizes. However, these patients are rare, Islam concludes.