Dr. O'Brien on Sequencing Small Molecule Inhibitors in CLL

Susan M. O’Brien, MD, hematologist/oncologist at University of California, Irvine Health, discusses sequencing small molecule inhibitors in chronic lymphocytic leukemia (CLL).

Ibrutinib (Imbruvica) is currently the only small molecule inhibitor with a frontline label, so that tends to be the preferred frontline agent. Although, there is a role for chemotherapy, explains O’Brien. Many physicians will use duvelisib and fludarabine-cyclophosphamide-rituximab (FCR) who have a mutated IGHV gene, as many studies have shown a plateau on the progression-free survival curve in patients with a mutation in IGHV. However, where physicians do not want to use FCR, ibrutinib will be used, says O’Brien. This decision is often based on mutation status as well as 17p deletion status, as chemotherapy is ineffective in patients with 17p deletion.

If the patient is intolerant to ibrutinib, idelalisib (Zydelig) plus rituximab (Rituxan) or venetoclax (Venclexta) can easily be adopted, explains O’Brien. However, patients who are refractory to ibrutinib may not experience lasting response with idelalisib. Whereas, venetoclax in the setting of ibrutinib resistance can induce durable responses alongside minimal residual disease negativity, says O’Brien.