ICML 2025 | Long-term outcomes of patients with Waldenström’s macroglobulinemia who discontinue BTKi therapy

This is a study conducted at MD Anderson where we looked at all patients over the past 10 years treated with BTK inhibitor therapy. We included all patients who received at least one cycle of therapy and what we found was that amongst patients who discontinued therapy, about half of the patients discontinued because of adverse events. Majority of those were infections, cardiopulmonary toxicity, importantly bleeding as well as atrial fibrillation. And the other half, about a quarter discontinued due to transformation or disease progression and another quarter discontinued because of patient or physician preference. Amongst those who discontinued and received a subsequent line of therapy, we found that if the reason for discontinuation was progressive disease, the outcomes are fairly equivalent based on the next line of therapy. Next line of therapies included a combination of rituximab with chemotherapy, another BTKi, venetoclax, or some sort of other clinical trial-based therapy. And when we looked at progression-free survival and overall survival outcomes in those patients, outcomes are fairly equivalent amongst those groups, so the overall response rate is around 60%. Specifically, if we looked at all patients who discontinued and then received another line of therapy, that’s including those who had an adverse event, we found improved PFS outcomes with a second BTKi. So the important takeaways were, if a patient discontinues because of an adverse event or other reason, it’s reasonable to consider another BTKi-based therapy. But if they have disease progression on a BTKi, we see pretty equivalent outcomes with the next line of therapy. So there’s a number of different options that can be selected for these patients.

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