Novel Therapies in CLL

Nicole Lamanna, MD:What’s great about this ASH [American Society of Hematology] meeting is that there are many things that have been highlighted, and I think one of the take-home points for oncologists in general is that there were 2 key presentations looking at ibrutinib in frontline therapy, whether for older folks or younger folks. And I think now people always ask does that mean chemoimmunotherapy is dead? Both of these studies were significant for ibrutinib, favoring the ibrutinib arms. And so I think one key take-home message from the meeting is that a novel BTK [Bruton tyrosine kinase] inhibitor can be used for anybody with CLL [chronic lymphocytic leukemia].

Now, there are some caveats to this. One of the things that folks always ask about is are younger folks who have favorable prognostic markers such as the mutatedIGVH. Can those guys still receive chemoimmunotherapy? I think that still remains an unanswered question because both of these studies did not necessarily favor ibrutinib over chemoimmunotherapy in the mutated folks. So I think that’s one discussion that oncologists can still have with their patients. And so that’s a highlight: If you are mutated and have favorable characteristics, could you still use chemoimmunotherapy? I think you can.

But there’s no doubt I think this solidifies the usage of ibrutinib in all patients, whether they’re old or young or have high-risk features. For sure, I think patients who have either 17p or p53 deletion or who are unmutated, we would favor an ibrutinib combination. And so I think that’s 1 highlight that oncologists also need to take home. If the patient has adverse features, you really should be favoring novel therapies over chemoimmunotherapy. And that’s another take-home point.

There’s obviously lots of new and exciting data that got presented at this meeting, looking at whether there should be combinations of novel agents. A lot of information regarding minimal residual disease was presented at this meeting, so we can talk more about that. And then we have the question of sequencing. So I think this is 1 unmet need in CLL. Currently with all these great new therapies that have emerged over the past several years, such as ibrutinib, and venetoclax, the PI3-kinase inhibitors, the question is how do we sequence these agents? If ibrutinib is started on most patients in the frontline therapy, then what do you after? What do you do subsequently? And so I think the meeting highlighted some of the things we can do post-ibrutinib, but I think we still need long-term follow-up data.

But there were several exciting presentations looking at after ibrutinib if somebody has progressed. If they’re intolerant to ibrutinib, can you go on to a different B-cell receptor agent or do you go to a Bcl-2 inhibitor like venetoclax? So I think there’s lots of different ways to proceed forward, and we’re going to need some long-term data about that.

Transcript edited for clarity.