Dr. Zelenetz on Treatment for Patients With CLL Who Fail on Ibrutinib or Idelalisib

Andrew D. Zelenetz, MD, PhD
Published Online: Tuesday, Jan 03, 2017



Andrew D. Zelenetz, MD, PhD, medical director of Quality Informatics at Memorial Sloan Kettering Cancer Center, discusses treatment options for patients with chronic lymphocytic leukemia (CLL) who fail on ibrutinib (Imbruvica) or idelalisib (Zydelig).

There are 2 ways to fail a kinase inhibitor, Zelenetz explains. One is to progress and, he adds, if a patient progresses on ibrutinib, switching to the other kinase inhibitor likely will not be an effective option. This was reported by Anthony Mato, MD, from a retrospective study presented at the 2015 ASH Annual Meeting.

Secondly, patients can fail a treatment if they are intolerant of the drug. Patients may come off of ibrutinib if they experience severe muscle cramping. Or, they may have diarrhea on idelalisib that is intolerable. In that situation, switching to the alternative kinase inhibitor is a viable treatment strategy, he says.

However, for patients who are progressing on ibrutinib and idelalisib, early evidence suggests that single-agent venetoclax (Venclexta) is effective in this group of patients and is associated with with very high response rates. In a study presented at the 2016 ASH Annual Meeting, results showed that a number of patients achieved minimal residual disease with venetoclax.


Andrew D. Zelenetz, MD, PhD, medical director of Quality Informatics at Memorial Sloan Kettering Cancer Center, discusses treatment options for patients with chronic lymphocytic leukemia (CLL) who fail on ibrutinib (Imbruvica) or idelalisib (Zydelig).

There are 2 ways to fail a kinase inhibitor, Zelenetz explains. One is to progress and, he adds, if a patient progresses on ibrutinib, switching to the other kinase inhibitor likely will not be an effective option. This was reported by Anthony Mato, MD, from a retrospective study presented at the 2015 ASH Annual Meeting.

Secondly, patients can fail a treatment if they are intolerant of the drug. Patients may come off of ibrutinib if they experience severe muscle cramping. Or, they may have diarrhea on idelalisib that is intolerable. In that situation, switching to the alternative kinase inhibitor is a viable treatment strategy, he says.

However, for patients who are progressing on ibrutinib and idelalisib, early evidence suggests that single-agent venetoclax (Venclexta) is effective in this group of patients and is associated with with very high response rates. In a study presented at the 2016 ASH Annual Meeting, results showed that a number of patients achieved minimal residual disease with venetoclax.



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