OncLive: How would you assess the current treatment spectrum for CLL? What are the most prominent management challenges?Woyach:
Jennifer A. Woyach, MD
We have a number of outstanding management options for patients with CLL right now, with multiple targeted therapies showing great success. In the frontline, our challenge now is to determine whether these therapies are best used in sequence or in combination. Phase III clinical trials–A041702 [NCT03737981] and EA9161 [NCT03701282], specifically–are trying to address this question. These trials are investigating ibrutinib/obinutuzumab with indefinite ibrutinib versus ibrutinib/venetoclax/obinutuzumab. In A041702, in older patients, those on the triple-therapy arm will have ibrutinib discontinued in a response-adapted manner,1
and in EA9161, for younger patients, ibrutinib will be discontinued in all patients.2
Also, we still have real needs to develop new therapies for patients who relapse after Bruton tyrosine kinase [BTK] inhibitors and venetoclax, as well as for those patients who develop Richter transformation.Can you discuss the goals and the rationale for the design of the ALLIANCE trial, on which you served as lead investigator?
[In the ALLIANCE trial] our goal was to determine whether ibrutinib was better than our best chemoimmunotherapy regimen in CLL, and to determine whether the drug was best alone or in combination with rituximab.3
At the time the trial was designed, we had excellent data on ibrutinib from single-arm clinical studies, mostly in relapsed/refractory disease. The RESONATE-2 study was getting started, and we knew that [it] was going to be comparing ibrutinib with chlorambucil, which was a test that ibrutinib was sure to win, but it still didn’t answer the question of whether ibrutinib was better than standard treatment.
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