ASH 2024 | Evolving treatment for WM: moving away from chemotherapy and toward fixed-duration combinations

I think although we know that our chemotherapy is still an important tool in treating and managing Waldenstrom’s disease, there’s a clear move towards omitting chemotherapy and trying to avoid chemotherapy-associated toxicities, also late toxicities. We know from retrospective studies that for instance, bendamustine can cause secondary neoplasias up to 17-18% depending on the data set. So this is why we move to chemotherapy-free approaches and at the moment for sure covalent BTK inhibitors are standard, zanubrutinib or ibrutinib, ibrutinib in combination with rituximab. But we have also venetoclax which might be a very important partner for covalent BTK inhibitors to give these drugs for a fixed duration for one or two years only and to avoid this continuous treatment we are doing at the moment. So, and here at ASH there are several presentations which follow this concept. So, one concept is our own study in treatment-naive Waldenstrom’s macroglobulinemia where we try to analyze the safety and efficacy of ibrutinib-rituximab in combination with bortezomib in this academic trial where we have seen best responses with major response rates of 98% and deep responses in 50% of patients. There’s another presentation with an update of the combination of ibrutinib, venetoclax, and another presentation which shows early results of pirtobrutinib plus venetoclax in Waldenstrom’s disease and I think this nicely reflects where we are going in Waldenstrom’s macroglobulinemia.

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