ASH 2025 | STAIR: time-limited acalabrutinib monotherapy in frail patients with previously untreated CLL

At ASH, I have presented the STAIR trial addressing an important point. Over the past decade, the BTK inhibitors have been transformative for patients with CLL. However, the continuous administration of these molecules could be associated with accumulation of adverse events over time that can be particularly detrimental in elderly patients. So the STAIR trial has evaluated the discontinuation of acalabrutinib in frail patients. So our study has enrolled 160 patients aged 70 years or older, and having comorbidities, defined as a SEER score greater than 6, and impaired creatinine clearance. So all the patients received acalabrutinib 100 milligrams twice daily for 18 months, and were then randomized to either arm A, in which the treatment was continued, and arm B, in which the treatment was discontinued. The primary endpoint was the PFS. And the result of this primary endpoint is that when we stop acalabrutinib, we have a one-year PFS rate of 53.1%, which fell below the pre-specified statistical assumption of the study that was 75%. So the study did not meet its primary endpoint. But that being said, there are three important findings. First, among the patients progressing after acalabrutinib discontinuation, 32.4% did not require a new line of therapy, with a one-year time to next treatment to restart the treatment of 74%. In this trial, we restart the treatment with acalabrutinib in patients presenting a symptomatic relapse after an independent committee review. And in these patients, we have seen that the overall response rate was 87.5%, with only one patient progressing after acalabrutinib discontinuation. So we can successfully restart the treatment. And for patients with discontinuing acalabrutinib, we did not see an impact on overall survival. And when checking among risk subgroups, we have seen that patients with mutated IGHV maintained favorable outcomes even after acalabrutinib discontinuation, which was not the case in patients with unmutated IGHV. So finally, there is no data supporting stopping the treatment after 18 months. But in some patients, this remains to be determined, patients with mutated IGHV, and we need a longer follow-up to determine if we have no negative impact on overall survival and if we can still restart the treatment successfully.

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