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ICML 2021 | Overcoming resistance in CLL

Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany, provides an overview of novel treatment regimens to treat resistance in chronic lymphocytic leukemia (CLL). Resistance to targeted therapies occur more frequently in relapse therapy than in frontline therapy, with repeated treatments in patients exacerbating the issue. Updates from the Phase II CAPTIVATE trial (NCT02910583) and the Phase III GLOW trial (NCT03462719) will assess the efficacy of ibrutinib plus venetoclax as a combination therapy in preventing resistance mutations in CLL. This is interview took place during the 2021 International Conference on Malignant Lymphoma (16-ICML).

Transcript (edited for clarity)

We are learning right now a lot about resistance, that they occur more frequently to the targeted agents and relapse situation than in frontline treatment. However, with continuous treatment with BTK inhibitors in frontline, they seem to be rare, but of course, with the duration of treatment we expect that they are becoming more frequent. We see them also with continuous treatment with venetoclax and also with time limited treatment relapse situation...

We are learning right now a lot about resistance, that they occur more frequently to the targeted agents and relapse situation than in frontline treatment. However, with continuous treatment with BTK inhibitors in frontline, they seem to be rare, but of course, with the duration of treatment we expect that they are becoming more frequent. We see them also with continuous treatment with venetoclax and also with time limited treatment relapse situation. What we do not yet know is about resistance mutations with time-limited treatment with venetoclax plus obinutuzumab. So relatively short duration of treatment.

So far it’s assumed that those patients can also be retreated. And then after these relatively short term intervals of 12 months with the treatment.

However, we are collecting right now, data on retreatment with venetoclax and, I think more interestingly, we even also with data shown at the ICML meeting update on the CAPTIVATE trial and also data from the GLOW trial in the late breaking abstract session of EHA and with the upcoming approval of the combination of ibrutinib plus venetoclax, the development of resistance to these targeted agents is crucial because that will determine how frequently we can retreat patients in the future and can re-expose those patients and still having efficient and treatment options in CLL patients available. So combinations of treatment is maybe one very good goal to prevent resistance mutations, but we need, of course, clinical data for proving that.

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