Susan O'Brien, MD

Susan O’Brien, MD, Associate Director for Clinical Science, Chao Family Comprehensive Cancer Center, University of California Irvine Health, put the venetoclax (Venclexta) monotherapy study in context. “The study by Jones et al is impressive. Patients who fail on a prior kinase inhibitor—idelalisib (Zydelig) or ibrutinib (Imbruvica)—have an overall response rate of 60% to 70% and an impressive 12-month progression-free survival of 80%.”

“The reason this is impressive is that a recent study by Mato et al showed that truly resistant patients who switch from one kinase inhibitor to another have a median progression-free survival of 7 months.¹ Jones et al are showing a 12-month progression-free survival of 80%,” she continued.

“Based on these data, if a patient fails ibrutinib, you would probably move on to venetoclax, with the caveat that venetoclax has a narrow label for relapsed 17p-deleted chronic lymphocytic leukemia [CLL]. In my experience, the labeling is not rigidly enforced, and I’ve been able to use venetoclax in that setting and get insurance to cover it, but I’m not sure how that plays out in the rest of the country,” she revealed.

Still a Role for Chemotherapy?

Other choices for a patient who relapses or is refractory to ibrutinib include idelalisib or chemotherapy. Dr. O’Brien pointed out that although ibrutinib is being used upfront in CLL, there is still a role for chemotherapy with fludarabine/cyclophosphamide/rituximab (FCR) in younger fit patients with a mutated immunoglobulin heavy-chain variable region (IGVH) gene.

“Three different studies have shown excellent results with front-line FCR in this patient group. At 12 to 15 years out, 60% of IGVH-mutated patients treated with FCR have no evidence of disease, and probably there is a cured fraction among them. Maybe upfront ibrutinib could cure them too, but we don’t have long enough follow-up to show that.”

According to Dr. O’Brien, however, there is rarely a reason to give chemotherapy in the relapsed setting. ■

Disclosure: Dr. O’Brien has consulted and received honoraria from AbbVie, Janssen, and Pharmacyclics as well as research funding from Pharmacyclics.

Reference

1. Mato AR, Nabhan C, Barr PM, et al: Outcomes of CLL patients treated with sequential kinase inhibitor therapy: A real world experience. Blood 128:2199-2205, 2016.