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

Susan M. O'Brien
Published: Monday, Aug 06, 2018



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.


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.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions & New Answers to Optimize OutcomesAug 16, 20181.5
Community Practice Connections™: Personalized Sequencing in Castration-Resistant Prostate Cancer: Bridging the Latest Evidence to the Bedside in Clinical ManagementAug 25, 20181.5
Publication Bottom Border
Border Publication
x