Jacqueline C. Barrientos, MD, MS, associate professor, The Feinstein Institute for Medical Research, Northwell Health, discusses remaining challenges in the treatment of patients with chronic lymphocytic leukemia (CLL).

Researchers do not have much data on sequencing strategies. For example, it is still unclear if a patient who has been exposed to venetoclax (Venclexta) can be salvaged with ibrutinib (Imbruvica) or idelalisib (Zydelig). Another challenge is determining optimal combinations, Barrientos says. If a patient is treated with venetoclax plus ibrutinib in the frontline setting, what is best to use in the second-line setting? PI3K-delta inhibition and CAR T-cell therapy, among other strategies, have potential. Recent progress has allowed physicians to shy away from chemotherapy, but it remains unclear what to do when patients become refractory to novel agents, says Barrientos.

Another challenge is the duration of therapy. TKI therapy is continued until a patient develops disease progression or a treatment-limiting toxicity. This is particularly hard for a young, fit patient who may be on therapy indefinitely. Ongoing trials are looking at combination strategies to define time-limited therapy, says Barrientos.