“Hypomethylating agents (HMAs) are the standard of care for patients with higher-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML), not eligible for intensive chemotherapy or allogeneic stem cell transplantation. However, the majority of patients do not respond to these agents. Patients failing HMA therapy still have a dismal outcome with very limited treatment options available.”
A New Treatment Option
Bemcentinib (BEM) is a small molecule that inhibits AXL. This membrane protein (AXL) is responsible for resistance to chemotherapy and is overexpressed on leukemia cells. AXL inhibition is a great target to attack for HR-MDS or AML patients.
In a multiphase trial, bemcentinib was used for patients who had experienced relapse or refractory disease who had received at least 4-6 cycles of either azacitidine or decitabine. Patients received:
- An initial dose of 400mg, orally administered on days 1-3 of cycle 1.
- Maintenance dose of 200mg, administered on days 4-28 of cycle 1.
- 200mg was administered on days 1-28 on repeated cycles of 28 days.
- The average age of patients was 79.
54 patients were enrolled in the trial (MDS=27, AML=31). Treatment was well tolerated, adverse effects were mostly: infections, toxicities and gastrointestinal disturbances. Preliminary results on AXL inhibition were more effective in MDS patients (66% responded positively).
Drug Combination Treatment
“Data also indicates that treatment with the bemcentinib-LDAC (dose cytarabine) combination shows promising efficacy in relapsed patients who are unfit for intensive chemotherapy.”
Notable positive results were seen in treatment weeks 20-28. “These later onset responses may reflect the importance of AXL-related immunological mechanisms for relatively chemo-resistant relapsed patients and contribute to a longer time-on-treatment.”
The primary overall response rate (ORR) was met with the MDS group achieving a 36% response rate and 8.3% of AML patients achieved stable disease. A comprehensive look at bemcentinib and its effective use in the treatment of these cancers is ongoing.
about the author
Lisa Foster is a mom of 3 daughters, a puzzle lover, writer and HealthTree advocate. She believes in the mission of the foundation and the team that builds it forward. She calls Houston, Texas home.