ICML 2025 | Treatment approaches for symptomatic, treatment-naive WM versus previously treated patients

For treating symptomatic treatment-naive patients, we tend to prioritize BTK inhibitors. Really our approach to treating patients is that do no harm and we are concerned about long-term consequences of alkylator therapies. We did hear at the last workshop on Waldenström’s in Prague, the update on the long-term results of the FILO study from France of patients who got bendamustine rituximab as their initial therapy. And the concern around that study was half the patients had long-lasting cytopenias and 18% of patients had secondary malignancies, some of which might be age-related, but treatment-related MDS and AML were also described in their study. So “do no harm” is very important, especially in a disease like Waldenström’s. We have now non-chemotherapy options, non-alkylator-based options. This is our priority for treating treatment-naive patients. But for patients who might have bulky adenopathy or amyloid, we do consider bendamustine as well as proteasome inhibition. In previously treated patients, it really comes down to what the patients have seen beforehand. Again, if the patient hasn’t seen a BTK inhibitor, consider that. But if the patient has progressed on a covalent BTK inhibitor, just know that pirtobrutinib, as well as venetoclax, are very, very active agents. And always think about a clinical trial, because the only way we’re going to make progress is by getting patients on clinical trials.

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