SOHO 2024 | The role of covalent BTKis in the management of CLL

I was discussing the role of covalent BTK inhibitors because in the last few years, they radically changed the management of patients with chronic lymphocytic leukemia. And now we know that in the long term they are very effective, meaning that they lead to an improvement in the overall survival of patients with chronic lymphocytic leukemia, regardless of age and comorbidity profile, but they are associated with some potential adverse events. We want to manage it best in order to improve also the quality of life of our patients. So covalent BTKis are meant to be taken as continuous treatment. And the main issues with continuous treatment is that you have long term exposure also to the risk of adverse events, including cardiac adverse events. So we started using ibrutinib, first in class BTK inhibitor, but in the last few years, second generation BTK inhibitors became available and they are more selective in their inhibition profile. So if we look at the kinase selectivity profile, we can identify the more selective profile. And this helps in reducing the risk of some adverse events including atrial fibrillation, hypertension, bleeding events. So in the end, nowadays the use of continuous BTK treatment is still a valuable option and we are doing that in many patients because it’s very convenient, it requires less frequent access to the hospital in order to check the blood test, the pills that can be taken every day at home. But in the long run, we are probably trying to improve the efficacy by combining different clans of agents in order to stop treatment at some point and reduce on one side the risk of developing adverse events and on the other side the risk of developing resistance.