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iwCLL 2021 | Interim analysis of the ALPINE study

Barbara Eichhorst, MD, of the University Hospital Cologne, Cologne, Germany, talks on the interim analysis of the Phase III ALPINE study (NCT03734016) which is investigating zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The interim analysis incorporated data from 400 patients. The primary endpoint was progression-free survival (PFS) and the most important secondary endpoint was the incidence of atrial fibrillation. Non-inferiority of zanubrutinib was demonstrated; however, Dr Eichhorst explains that the median follow-up was only 15 months, hence, a longer follow-up is required before a judgement on the superiority of one agent can be made. This interview took place at the 19th International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Biennial Meeting, held virtually in 2021.

Transcript (edited for clarity)

The ALPINE study is a randomized Phase III trial in relapsed CLL patients with a head-to-head comparison of continuous treatment of the BTK inhibitor ibrutinib versus the newer BTK inhibitor zanubrutinib. Patients were included if they had at least one prior therapy and with respect to that, most patients were not heavily pretreated and altogether 600 patients were included; however, the interim analysis was based on 400 patients who were included initially and then there came an amendment for including additional 200 patients for the detection of overall survival benefit; however, the first primary endpoint, which was the non-inferiority with respect to progression-free survival on the 400 patients, was met right now, showing non-inferiority of zanubrutinib which has to be taken twice a day in contrast to ibrutinib being taken once a day...

The ALPINE study is a randomized Phase III trial in relapsed CLL patients with a head-to-head comparison of continuous treatment of the BTK inhibitor ibrutinib versus the newer BTK inhibitor zanubrutinib. Patients were included if they had at least one prior therapy and with respect to that, most patients were not heavily pretreated and altogether 600 patients were included; however, the interim analysis was based on 400 patients who were included initially and then there came an amendment for including additional 200 patients for the detection of overall survival benefit; however, the first primary endpoint, which was the non-inferiority with respect to progression-free survival on the 400 patients, was met right now, showing non-inferiority of zanubrutinib which has to be taken twice a day in contrast to ibrutinib being taken once a day.

The median follow-up of this trial was 15 months. It’s very short, therefore, so, the curves looked really very interesting, because the zanubrutinib curve right now seems to do a lay over, so being better than ibrutinib, but I think it’s too early here with this very short follow-up for a final judgment and I think we should also wait until we have more data from the other 200 patients, so 600 patients in total.

In addition to that, the most important secondary endpoint was the incidence of atrial fibrillation. And here we see already a clear trend, but the incidence is less frequent with zanubrutinib in contrast to ibrutinib, which is explained by the more selective binding of zanubrutinib to BTK and not hitting so many other targets as we know that from ibrutinib.

So, we see an alternative BTK inhibitor in relapse situation having at least similar efficacy and leading to a lower incidence of atrial fibrillation.

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Disclosures

Barbara Eichhorst, MD, has participated in consultancy and/or advisory boards with Janssen, Roche, Novartis, AbbVie, Gilead, Celgene, ArQule, AstraZeneca, Oxford Biomedica (UK), MSD and Miltenyi; has received speaker’s bureau from Janssen, Gilead, Roche, AbbVie, Novartis, Celgene, AstraZeneca, Adaptive Biotechnologies and Hexal; has received research funding from Janssen, Gilead, Roche, AbbVie, BeiGene and Astra Zeneca; and ha received travel, accommodation and/or expenses from Janssen, Roche, Novartis, AbbVie, Gilead and Celgene.