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ASH 2025 | Fatigue, Hb, & inflammatory markers in patients with wAIHA treated with rilzabrutinib in LUMINA2
In this video, David Kuter, MD, Massachusetts General Hospital, Boston, MA, discusses an analysis of data from the LUMINA2 study (NCT05002777), which investigated the use of rilzabrutinib, a BTK inhibitor, for the treatment of warm autoimmune hemolytic anemia (wAIHA). Prof. Kuter highlights that a significant hemoglobin (Hb) response was observed in over half of patients treated, with increases in Hb and declines in inflammatory markers correlating with subsequent improvements in fatigue scores. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
So the LUMINA2 study used a Bruton kinase inhibitor called Rilzabrutinib to treat warm antibody hemolytic anemia. This is a disease state for which there are many therapies, very few of which work and provide remission. The standard of care is corticosteroids and rituximab, which works for maybe a third of the patients. And so many patients have a, in quotation marks, unmet medical need for having a better therapy...
So the LUMINA2 study used a Bruton kinase inhibitor called Rilzabrutinib to treat warm antibody hemolytic anemia. This is a disease state for which there are many therapies, very few of which work and provide remission. The standard of care is corticosteroids and rituximab, which works for maybe a third of the patients. And so many patients have a, in quotation marks, unmet medical need for having a better therapy. Rilzabrutinib, by being a BTK inhibitor, turns off macrophages, and it decreases the rate of phagocytosis of red cells. And so we’ve given this to 41 patients, and what was striking is that more than half the patients responded with a rise in hemoglobin over two grams, and then they went on to a longer-term study, and most of those patients were able to maintain that response for another 24 weeks.
So we’ve got a one-year study looking at patients, mostly responders, which is more than half the patients. And we asked what happens with the hemoglobin, and did it correlate with the fatigue scores? And so fatigue is a very common component of anemia. When these patients had a higher hemoglobin, their fatigue scores improved dramatically over baseline. And then we asked, did that fatigue score improve over a whole 54 weeks of study? And it did. So patients had a nice response. And in general, the responders with a rise in hemoglobin that correlated well with fatigue increases. We then looked at whether fatigue is caused by various cytokines that might be affected by this drug. And rilzabrutinib, by inhibiting Bruton kinase, can turn off cytokine pathways. And so what we learned is that in patients who got this medication and responded, their levels of IL-10, interferon alpha, and also TNF declined dramatically, and as those levels declined, their fatigue scores improved, so implying that the fatigue was in part related to the generation of these cytokines. So in summary, this manuscript is interesting because it shows that there’s a new therapy for warm antibody hemolysis, which is effective in raising hemoglobin, but more importantly, turns off other components of the inflammatory cascade, which may be contributing to the fatigue these patients experience.
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