ASH 2021 | ASCEND: 3 year follow-up of acalabrutinib in R/R CLL

So the ASCEND trial is a Phase III study, where patients with chronic lymphocytic leukemia in the relapsed or refractory setting have been randomized to either acalabrutinib monotherapies, continuous therapy, or a physician choice between bendamustine plus rituximab, or idelalisib plus rituximab. 155 patients were randomized to acalabrutinib monotherapy. 155 patients were randomized to the physician choice. But the vast majority, 119, have chosen to be treated with idelalisib plus rituximab, making this study the first, and probably the only one, comparing a BTK to a PI3-kinase inhibitor. At ASH, Dr. Wojciech Jurczak presented the three-year follow-up of the ASCEND study, where indeed, we confirmed the long-term benefit in terms of PFS, progression-free survival, for patients who have been treated with acalabrutinib. In particular, 63% of the patients treated with acalabrutinib were free of progression or death after three years of follow-up, while instead, of the patients who have been treated in the physician choice arm, only 21% of them were free of progression, and in particular, 25% if treated with idelalisib plus rituximab, and 9% if treated with bendamustine plus rituximab.

This difference in PFS was probably also due to the fact that patients who received idelalisib plus rituximab more frequently discontinued the drug because of adverse events, and therefore, they could not benefit in the long run from the efficacy of the drug. So with this trial then, which is a seminal trial, it has been utilized for the approval of the drug worldwide. Also, in the relapsed or refractory setting, we indicate the treatment, the continuous treatment with a BTK inhibitor, like acalabrutinib, is very effective also in the long term, and also very safe. And indeed again, as in many other trials, acalabrutinib showed low frequency of atrial fibrillation, low frequency of hypertension, and low frequency of minor bleedings.