Covalent BTK Inhibitors in Relapsed/Refractory CLL

EP: 1.Mechanism and Frontline Use of BTK Inhibitors in CLL

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EP: 2.Covalent BTK Inhibitors in Relapsed/Refractory CLL

EP: 3.Comparing BTK Inhibitors: Key Findings from Head-to-Head Trials

EP: 4.Clinical Considerations for BTK Inhibitor Treatment Selection

EP: 5.Molecular Mechanisms of Resistance to Acalabrutinib in CLL

EP: 6.Treatment Options for Patients with CLL Progressing on Covalent BTK Inhibitors

Dr. Brian Hill: So let's turn. So that's sort of a broad overview of frontline treatment. Maybe we can talk a little bit about how you approach a patient with relapse or refractory CLL in the current era.

Dr. Paul Ghia: Yes. Now, guidelines are sometimes already still keeping into account the use of immuno chemotherapy as a frontline. So the choice in second line becomes easy. It's a novel therapy by definition. I think that nowadays nobody thinks of repeating chemo immunotherapy in a patient who already received chemotherapy in frontline. bendamustine rituximab was a typical second choice, second line three 20 patient with CLL. But now we know that at maximum we can get to 18 months of response in our patient. That's the median progression-free survival that we see in all trials where indeed the novel therapies have been tested and BTK inhibitors have been tested against bendamustine rituximab. So if frontline was therapy was a chemo immunotherapy, it's easy. If in frontline, the patients already receive a novel therapy, it really depends what received. So most patients still now, they receive a BTK inhibitor, continuous BTK inhibitor. So the obvious choice will be venetoclax plus rituximab has, that has been shown in the MURANO studies that is better than, BR, bendamustine rituximab, both in terms of PFS, progression-free survival and overall survival. If someone has been treated, as you mentioned with venetoclax obinutuzumab in frontline fixed duration, it remains to be explored if the patient can be retreated again, with venetoclax there is not so much data. Data is accumulating thanks to the CLL 14 study. But at the moment, probably the preferred option would be to switch, to go treat with a BTK continuous BTK inhibitor.

Dr. Brian Hill: Yes, and certainly the MURANO trial was comparing chemoimmunotherapy versus venetoclax with rituximab, but I think most of those patients had not been previously treated with BTK inhibitors. So that's a great evidence for the use of venetoclax after chemoimmunotherapy. And we do have some real-world evidence of the efficacy of venetoclax after frontline BTK.