At EHA this year in the virtual edition we discussed and presented the final results of the ASCEND study which is an international phase III randomised study where patients with relapsed and refractory CLL have been randomised to either be treated with acalabrutinib monotherapy or with a physician’s choice between idelalisib plus rituximab or bendamustine plus rituximab.

Out of the 310 patients who have been enrolled 155 were treated with acalabrutinib monotherapy while the other 155 were treated with physician’s choice, the vast majority with idelalisib plus rituximab, 119 patients while only 39 patients were treated with bendamustine plus rituximab.

In the final analysis we confirm the benefit in terms of progression free survival after a longer follow-up, a median of 22 months, so with an additional six months compared to the last presentation of the interim analysis. The PFS of acalabrutinib is an estimated 18 months, a PFS of 82% compared to 48% of the physician’s choice arm. This benefit is also maintained in the patients with high risk genetic features, so both in patients with 17p deletion and/or p53 mutation but also in patients with unmutated immunoglobulin genes.

Remarkably, at this point there is no advantage in overall survival also because we have to recall that the patients could indeed cross over from the physician’s choice arm to acalabrutinib in case of progression.

The efficacy of the drug in terms of safety, the longer follow-up did not show any unexpected adverse events and, indeed, the safety profile of acalabrutinib monotherapy is confirmed with a typical headache in one quarter of the patients, a headache which is short lasting. Then you can have also neutropenia or anaemia. Among the adverse events of clinical interest, atrial fibrillation was present in 6% of the patients and haemorrhage was interestingly in less than one-third of the patients, 29%, with major haemorrhage in only 3%. Hypertension was also low in 5% of the patients and then we had second primary malignancies in 5% of the patients.

So, in conclusion, the final results from ASCEND confirm the findings at the interim analysis and support, indeed, a favourable efficacy and safety of acalabrutinib monotherapy in comparison to the standard treatment for relapsed/refractory CLL, on one side a chemo-free treatment like idelalisib plus rituximab, on the other side a classic traditional immunochemotherapy regimen like bendamustine plus rituximab.

Thank you very much for your attention.