What follows is our patient-friendly summary of this research.
The Bottom Line:
BMF-219, an irreversible menin inhibitor that demonstrated strong preclinical activity against chronic lymphocytic leukemia or CLL patients’ specimens, including those with high-risk markers.
By whom and where were the research and presentation done:
Priyanka Somanath, Ph.D. at Biomea Fusion, and her colleagues presented the results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago in 2022.
Menin is a widely expressed protein found mainly in the cell’s nucleus. Among its many functions, it downregulates the expression of BCL-2, which is a good thing. BCL-2 is overexpressed in CLL and blocks programmed cell death or apoptosis. Blocking BCL-2 is how venetoclax works.
Methods and Participants:
A comprehensive panel of CLL samples isolated from patients with early to advanced disease, including relapsed or refractory disease, were cultured ex vivo or outside the body in the presence of BMF-219 to assess the antileukemic activity of the compound.
- BMF-219 demonstrated high potency, achieving > 98% cell lethality at one low exposure in all patient samples tested.
- Specimens isolated from patients with clinical profiles of high-risk genetic backgrounds associated with inferior outcomes to standard therapy, such as mutations in TP53 and NOTCH1, and chromosomal aberrations such as del(13q), trisomy 12 and complex karyotype, exhibited high sensitivity to BMF-219 treatment.
- BMF-219 was also highly effective against patient samples with clinical profiles of resistance to bendamustine, ibrutinib, and venetoclax therapy.
Conclusion and Comments:
BMF-219, an irreversible menin inhibitor, has promising preclinical data suggesting it might be a novel therapeutic option for patients with CLL.
For comparisons, all the specimens were also exposed to different reservable menin inhibitors with disappointing results.
Still, CLL cells are notoriously easy to kill in Petrie dishes and much harder to eliminate in patients’ blood, marrow, and nodes.
Fortunately, clinical trials for CLL are in development. CLL Society welcomes this research with an entirely novel mechanism to eliminate the cancer because, despite all the progress, CLL is not a solved problem.
Links and resources:
The ASCO 2022 abstract that gives more detailed statistics can be found here: Preclinical activity of irreversible Menin inhibitor, BMF-219, in chronic lymphocytic leukemia.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer, CLL Society, Inc.