ASH 2024 | The PreVent-ACaLL trial: treating patients with CLL who are at high risk of infections

So we have seen during the last few years publications from the CLL-12 trial testing preemptive treatment for patients with CLL without meeting the criteria for starting treatment based on iwCLL but being high-risk patients. These trials were positive but did not improve overall survival and it was not considered to change the treatment paradigm for patients with CLL. What we have done with the PreVent-ACaLL trial is to use a machine learning algorithm called CLL treatment infection model, identifying by this model the 20% of patients newly diagnosed with CLL who have more than a 70% risk of having a severe infection or needing CLL treatment within two years from diagnosis. The reason we did that was that we realized an unmet clinical need in terms of patients diagnosed with CLL who suffered from serious infections before meeting criteria to start treatment for CLL. And we wanted to change the immune dysfunction for these patients. And we are testing that in an ongoing clinical trial, the PreVent-ACaLL trial, where we treat patients with short duration of targeted treatment with acalabrutinib and venetoclax. And it’s randomized to standard of care, which would be observation. Primary outcome being safety but also as a secondary outcome monitoring the infection-free treatment-free survival for these patients. In parallel we assess the immune function for myeloid cells and T-cell subsets and the combined efficacy of the immune system in whole bloods from these patients. And what we see now is that during the treatment and after end of treatment for these free cycles of targeted agents with acalabrutinib and venetoclax. We see signs of improvement both in terms of T-cell functions, in terms of the myeloid compartment, and in terms of the combined efficacy of the immune system tested by TruCulture assays, where you do a standardized stimulation of the toll-like receptors and measure the cytokine release up in that stimulation. And why is that important? Because we want to change the natural history of immune dysfunction in CLL and we now have a plentitude of different treatment options, but we also have different criteria that we need to test both in the primary or first-line treatment, but also for secondary relapses to see when would we actually best start treatment to see if we could improve the immune function and in that way targets the major cause of death for patients with CLL still being infections.

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