Frontline Anti-CD20 Therapy in CLL


The rationale for integrating CD20 monoclonal antibody therapy into the frontline setting of chronic lymphocytic leukemia.

Susan O’Brien, MD: Now, what about adding in an anti-CD20? Are you doing that when you’re using BTK [Bruton tyrosine kinase] inhibitors? And maybe you can talk about the reason I’m asking you that, which is some recent clinical trial data.

Anthony Mato, MD, MSCE: So generally not in clinical practice, although I think the data from the ELEVATE-TN trial is intriguing. Just to review, that trial was a frontline trial looking at acalabrutinib plus or minus obinutuzumab vs chlorambucil/obinutuzumab. So 1:1:1 randomization. The acalabrutinib based therapies were better. Interestingly, the acalabrutinib/obinutuzumab had a PFS [progression-free survival] advantage over the acalabrutinib monotherapy, not only at the first interim analysis at 24 months, but those curves actually widened when they took a look 2 years later. Really supporting the fact that if you add obinutuzumab to acalabrutinib, there’s an advantage in PFS. Interestingly though, I would’ve predicted it would have been in the high-risk patients like this with the deletion [del] 17p. When you look at the data, the del 17p patients were really the only group that didn’t appreciate an advantage in PFS when the obinutuzumab was added. So for this patient, for sure I would give acalabrutinib as a monotherapy. Now, if you’re thinking about use of ibrutinib, unfortunately the ibrutinib/obinutuzumab trial iLLUMINATE did not include an ibrutinib monotherapy. So I just generally don’t really understand the relative contribution for the obinutuzumab to ibrutinib, so I give ibrutinib as a monotherapy no matter what. Then of course we have randomized data from the ALLIANCE trial, an MD Anderson Cancer Center-based randomized trial in the relapse/refractory setting, suggesting no clear role for adding rituximab to ibrutinib. So short answer is most of the time just as monotherapy is probably the right answer. In a high-risk patient, it seems to be the way to go.

Susan O’Brien, MD: If this patient did not have a 17p deletion, let’s say he had no abnormality in the FISH [fluorescence in situ hybridization], what would you? Would you give the antibody with the acalabrutinib or have you done that yet, or is COVID-19 impacting your thoughts about that?

Anthony Mato, MD, MSCE: So I’m a little biased in my answer because we have a frontline trial looking at acalabrutinib/obinutuzumab as a time-limited therapy. So I think the MRD [minimal residual disease] data from now extrapolating iLLUMINATE and a little bit of the MRD data we had from ELEVATE-TN really do support that obinutuzumab deepens remission responses to ibrutinib or acalabrutinib. That opens the window to me as a time-limited therapy, but that’s not standard of care. So most of my BTK starts in my practice have been on that trial. In clinical practice, most of the time I’m just giving acalabrutinib as a monotherapy at this particular moment. Of course the pandemic does have some influence over decision-making as there is some data to suggest that an anti-CD20 will blunt, partially blunt, or completely blunt the response to vaccines, not only to COVID, but to any particular virus that we’re immunizing against.

Susan O’Brien, MD: It was unfortunate for me that there were some of my patients I wanted to give venetoclax/obinutuzumab and I deliberately waited until they had 2 COVID shots and then started their treatment. Then what happened later, this third shot was recommended. I am very worried that those patients are not going to amount much to that third shot because of the use of the antibody in that setting. So it’s definitely tricky. I agree with you. I have not given obinutuzumab with acalabrutinib, but of course when that trial was first published, there was a little over 2 years of follow-up. At that point, the acalabrutinib and the acalabrutinib/obinutuzumab curve were slightly separate, but really nothing to write home about. As you pointed out over the 2 years more follow-up that we have, and we just got this data. This was at the spring meetings, ASCO [American Society of Clinical Oncology], EHOC [Eurasian Hematology-Oncology Congress], etc. We saw the 4-year data where those curves are fairly dramatically separated. So I haven’t done it up until now, because of course up until a few months ago, we had not seen such a large separation in the curves. It definitely wasn’t there at the 2-year mark. So I’m considering it. Although, again, right now, I think the impact would kind of push me against it, that’s still the ongoing issues with COVID in that sense. So I haven’t done it yet. I might consider it moving forward.

Transcript edited for clarity.

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