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iwCLL 2023 | EPCORE CLL-1: epcoritamab in patients with R/R CLL & Richter’s transformation
Arnon Kater, MD, PhD, University of Amsterdam, Amsterdam, Netherlands, discusses results from the EPCORE CLL-1 trial (NCT04623541), which is evaluating the safety and efficacy of epcoritamab in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and Richter’s transformation (RT). This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2023 meeting, held in Boston, MA.
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Transcript
So one and a half years ago we started at trial. It was a company sponsored trial to see whether bispecific antibodies, in this case CD3/CD20 epcoritamab will be effective in CLL and in Richter’s transformation. And that’s a maybe challenging path because we know that you have on one side, a lot of tumor cells in the blood, so you have bulky disease but in the leukemia form but you might cause maybe additional toxicities...
So one and a half years ago we started at trial. It was a company sponsored trial to see whether bispecific antibodies, in this case CD3/CD20 epcoritamab will be effective in CLL and in Richter’s transformation. And that’s a maybe challenging path because we know that you have on one side, a lot of tumor cells in the blood, so you have bulky disease but in the leukemia form but you might cause maybe additional toxicities. And on the other hand you have this T-cell dysfunction which is very characteristic of CLL. So it was a very exciting way of checking this. And what we have done is we treated now 23 patients with monotherapy, and those patients were very refractory so a lot of them were double exposed to BTK inhibitors and BCL2 inhibitors, the majority had 17p deletions or p53 aberrations. And what we did see is, if you first look at efficacy, is that it was very effective, I have to say, in this patient group. More than half of the patients got an overall response and approximately one third got a CR, and if you look to MRD data, you actually saw that all the patients with CR had undetectable MRD and half the patient with a PR got undetectable MRD. So I think for a monotherapy end of the road Phase I/Phase II trial, these are really remarkable numbers.
Then of course you do discuss side effects. So we did see patients with cytokine release syndrome which is a very typical side effect of bispecific antibodies but they were mostly grade one and two, very few had a grade three. They were all resolved and they all came very early and actually were pretty manageable. And the most cumbersome maybe side effect of this kind of treatment is ICANS, this is immune related neurotoxicity, we did see that in very few patients also and also that was manageable but that’s really what we think that for the future of this drug, we need to have a close eye on. And for the future, I think very much that it could be a very good drug to be given together with the targeted agents. So within the Hoven group, we’re going to do a trial with a venetoclax combination and one with a non-covalent BTK inhibitor.
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