New Immunotherapeutic Agents Broaden Treatment Options for Chronic Lymphocytic Leukemia - Episode 2

Treatment Strategies With Ibrutinib in CLL

Nicole Lamanna, MD:Two of the main presentations highlighted ibrutinib. One was presented by Jennifer Woyach, MD, and that was the Alliance [North American Intergroup] study that looked at untreated older patients with CLL looking at ibrutinib and rituximab versus bendamustine and rituximab. And, again, this I think solidifies the use of ibrutinib in older folks. The PFS, or progression-free survival, was better in the ibrutinib arms, and so there was no doubt that the ibrutinib arms were better than bendamustine/rituximab. There was the third cohort of ibrutinib/ritux [rituximab] versus ibrutinib. I think the addition of rituximab did not enhance ibrutinib alone as monotherapy. So when folks ask the question, does a monoclonal antibody need to be combined with ibrutinib, I think we have fair amount of data now that says maybe rituximab or another antibody doesn’t add all that much to ibrutinib, which may be different with venetoclax per se. But I think this trial highlights that the progression-free survival was better in the ibrutinib-containing arms.

The next larger study looked at the untreated but fit population. This is similar to the Jennifer Woyach study. This was the ECOG[-ACRIN Cancer Research Group] study, and this looked at fludarabine/cyclophosphamide/rituximab [FCR] or FCR versus ibrutinib/rituximab. And, again, for younger, fit patients, this was another example of ibrutinib that looked to answer the question of is chemoimmunotherapy better than ibrutinib. And here ibrutinib/rituximab again won out over the FCR arm, including increase in overall survival. Both progression-free survival and overall survival were better with ibrutinib than FCR, with that exception of the mutatedIGVHfolks. So it obviously was better for patients with high-risk features and patients who were unmutated, but the survival was not necessarily better in the patients who are mutated. So that question of can you still use chemoimmunotherapy or FCR in mutatedIGVHfolks is still reasonable, depending upon the patient’s preference. But you absolutely can talk about that with your patient. So whether chemoimmunotherapy or ibrutinib-containing regimen, I think both are probably acceptable until we have long-term data. And those were the 2 highlights.

The iLLUMINATE study was also presented at the meeting, and this was an update of ibrutinib and chlorambucil, but ibrutinib with obinutuzumab, and chlorambucil and obinutuzumab. Now, obviously, in the United States, chlorambucil isn’t used that commonly, and so the comparator arm of having chlorambucil and obinutuzumab compared to ibrutinib and obinutuzumab may not be something we would normally do. Clearly, the trial favored the ibrutinib arm, again highlighting ibrutinib over chlorambucil or chemoimmunotherapy. So that was also a significant finding, but again the comparator arm lacks a little bit of an interest for some of us. But certainly, it solidifies and highlights that an ibrutinib-containing regimen is better than a chemoimmunotherapy-containing regimen.

Transcript edited for clarity.