ASH 2025 | Phase II study of burixafor + propranolol + G-CSF for stem cell mobilization in myeloma

So, stem cell transplant is still standard of care for the treatment of multiple myeloma patients. Before we go to stem cell transplant, we have to mobilize stem cells for us to infuse them back into the patients. And the way we do that is currently with GCSF, so growth factor, and with a class of medications called CXCR4 inhibitors. Currently, we have two drugs in that class of medications that are approved by the FDA and that we use in the U.S., plerixafor and mozobil. So we have to achieve at least 2 million cells to proceed to transplant. So currently, with the stem cell mobilizers that we have, there are certain side effects to those medications, mostly diarrhea and infusion-related reactions and things like that. And also the peak stem cell mobilization happens kind of 10 to 12 hours after the drugs are given. So we have to give the drugs the day before the patients start collecting, which can create a little bit of inconvenience for patients and, you know, infusion centers. The other thing is right now we’re giving more and more daratumumab in the frontline setting for induction therapy for myeloma. There are certain studies that are actually suggesting that daratumumab may decrease the stem cell mobilization yield in certain patients. And so because of all those reasons, you know, the slow kinetics of stem cell mobilization, the side effect profile, and the lack of really prospective trials in the era of daratumumab and myeloma, we wanted to study a novel CXCR4 inhibitor called birexifor in combination with the beta blocker propranolol and with GCSF in myeloma patients. So we know from preclinical and some clinical studies that propranolol, which is a beta blocker, can actually inhibit beta-adrenergic receptors in the bone marrow, which can actually help shift the phenotype in our progenitor cells in the bone marrow from a more myeloid phenotype to a more stem cell phenotype, which is actually good, which may actually increase our stem cells in the bone marrow. So we decided to combine that drug with birexifor and GCSF, and we enrolled 19 patients on that study. We gave propranolol before stem cell collection, and then birexifor on the day of the stem cell collection. So this drug is a little different from the other medications that we have. So birexifor causes the stem cells to peak in the blood about an hour after the drug is infused. So it’s an IV infusion, and the stem cells actually peak one hour later, which is different from the other CXCR4 inhibitors that we have, where the peak mobilization happens after 10 to 12 hours. So it’s way faster. So the drug is given in the morning, IV on the day of collection, and then collection, apheresis, happens 45 minutes to two hours after. So it starts right away. We don’t have to really wait. What we found in that study was that 90% of the patients, or close to 90% of the patients, actually achieved the primary endpoint of at least two million cells collected for infusion for stem cell transplant in two apheresis sessions. So almost all of the patients collected enough to proceed to transplant in two apheresis sessions. And what was really interesting about this study was that the enrolled population, most of them had already received daratumumab before stem cell mobilization and collection, which is different from the prior CXCR4 inhibitors. The studies did not really enroll patients who received daratumumab. And 85% of the patients who received daratumumab and lenalidomide for induction, they achieved the primary endpoint. So most of the patients who received daratumumab actually did collect enough to proceed to transplant, which is very encouraging. The safety profile of the drug or the combination was very favorable. Most of the side effects were grade one and grade two, so low-grade side effects, most of them were related to GCSF, so the growth factor GCSF, so bone pain and back pain. We did see one case of infusion-related reaction that wasn’t, you know, high grade, it was low grade, and we did see one case of diarrhea, which is different again from the drugs that we have currently in the market. So this combination is really promising with a favorable safety profile, rapid kinetics of cells, more convenient schedule, and hopefully, it will proceed to further large studies.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.