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ICML 2025 | MAIC of ibrutinib versus other covalent BTK inhibitors in frontline CLL treatment
Alexey Danilov, MD, PhD, City of Hope, Duarte, CA, shares the findings of a matching-adjusted indirect comparison (MAIC) of ibrutinib versus acalabrutinib and zanubrutinib in patients with previously untreated chronic lymphocytic leukemia (CLL) using three pivotal trials: RESONATE-2 (NCT01722487), SEQUOIA (NCT03336333), and ELEVATE-TN (NCT02475681). Results demonstrated that progression-free survival (PFS) with ibrutinib was similar to acalabrutinib and zanubrutinib. This interview took place during the 18th International Conference on Malignant Lymphoma (18-ICML) in Lugano, Switzerland.
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Transcript
So today we have a choice which covalent BTK inhibitor we can use in previously untreated patients with chronic lymphocytic leukemia. So when we see a patient with CLL we have a choice between ibrutinib which is a less selective BTKi or so-called second-generation BTK inhibitors which have somewhat high selectivity towards BTK, and those are acalabrutinib and zanubrutinib. And ibrutinib was transformational in treatment of lymphoid malignancies, as this was the first drug approved among the BTK inhibitors in treatment of CLL...
So today we have a choice which covalent BTK inhibitor we can use in previously untreated patients with chronic lymphocytic leukemia. So when we see a patient with CLL we have a choice between ibrutinib which is a less selective BTKi or so-called second-generation BTK inhibitors which have somewhat high selectivity towards BTK, and those are acalabrutinib and zanubrutinib. And ibrutinib was transformational in treatment of lymphoid malignancies, as this was the first drug approved among the BTK inhibitors in treatment of CLL. So there are very many patients still being treated with ibrutinib in the United States and certainly in many other parts of the world. So, there have been several randomized studies in relapsed CLL. However, in previously untreated CLL, there are currently no randomized trials comparing ibrutinib versus other BTK inhibitors. And this is why we conducted a matched-adjusted indirect comparison of ibrutinib against acalabrutinib and zanubrutinib. So we used the pivotal trials RESONATE-2, SEQUOIA, and ELEVATE-TN to conduct this analysis. And the follow-up was, you know, almost 10 years with the ibrutinib and about 6 years with the other two drugs. So we adjusted the patient population to balance the patients as much as we could so that they have comparable characteristics when we conducted the comparison. And after adjusting for several variables, we came out with fairly balanced groups, of course, that reduced our patient numbers from initial roughly 120 per group to maybe 90 per group. But at the end of the day, what we observed is that progression-free survival with ibrutinib was very similar to acalabrutinib and zanubrutinib. And this is certainly encouraging for patients who continue treatment with ibrutinib at this time to know that the efficacy of this drug is comparable over time to that of selective BTK inhibitors.
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