BEXMAB Study: Dr. Amer Zeidan Remarks on the Results’ Meaning for MDS Care

Amer Zeidan, MBBS, MHS, is professor of internal medicine at Yale School of Medicine in New Haven, Connecticut. He is also the chief of the Division of Hematologic Malignancies at Yale Cancer Center, New Haven.

Dr. Zeidan spoke with Blood Cancers Today about the phase 1/2 BEXMAB study, which was presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, recently held in Chicago, Illinois, and will be presented at the European Hematology Association (EHA) 2025 Congress in Milan, Italy.

The BEXMAB study evaluates the combination of bexmarilimab, a macrophage Clever-1 receptor-targeting monoclonal antibody, with azacitidine to treat high-risk myelodysplastic syndrome (MDS). Expression of the Clever-1 receptor, Dr. Zeidan explained, is elevated in MDS and acute myeloid leukemia (AML), as well as in cancers in general, and in patients, it leads to inhibited macrophage activity against cancer cells.

“Through the development of [an] antibody against Clever-1 called bexmarilimab, this will convert the macrophages to a pro-inflammatory state, which allows them to increase the activity against the tumor cells, but also, it can activate the immune system through the T-cell adaptive response,” Dr. Zeidan said regarding the agent of focus in BEXMAB.

Phase 1 of the study was its dose-escalation component, which enrolled patients with frontline and relapsed or refractory MDS, and AML after hypomethylating agent (HMA) failure. The patients received three different doses of weekly bexmarilimab in the study combination. Phase 2, then, concerned dose optimization and enrolled patients with frontline and relapsed or refractory high-risk MDS with HMA failure.

Presented at the ASCO Annual Meeting were new safety and efficacy data from the BEXMAB study’s safety cohort of 53 patients who had high-risk MDS, 21 of whom were tested in the frontline setting and 32 in the relapsed or refractory setting. Dr. Zeidan described the enrolled cohort as being representative overall of the patients typically seen in the community setting.

“The patients in the HMA failure cohort had exposure to, at least, HMA and potentially additional agents like venetoclax, and some of them had prior transplant. I would note that many patients in the frontline setting, as well, have [a] TP53 [mutation], which we know makes the MDS more aggressive,” he elaborated.

From the dose-optimization phase, the BEXMAB investigators determined that a bexmarilimab dose of 3 mg/kg resulted in the best balance between safety and efficacy for patients. The combination was well tolerated by patients in the safety cohort, who had a low rate of discontinuation, no deaths related to the treatment, and a low rate of immune-related adverse events. Overall, the adverse events that occurred were manageable and as expected for the high-risk MDS patient population, with the most common being related to blood count suppression or fatigue.

The efficacy results with the combination were additionally encouraging. Among these were the International Working Group (IWG) 2023 criteria–based composite complete remission (CR) rate results, with benefit observed in both frontline MDS and relapsed or refractory disease and in patients with a TP53 mutation.

“Overall, we are kind of excited about this early efficacy data, and we also saw evidence of immune activation with bexmarilimab, as well as some evidence of correlation between Clever-1 expression and seen responses,” Dr. Zeidan mentioned.

Dr. Zeidan believes that the positive safety and efficacy performance of bexmarilimab plus azacitidine, such as that observed in BEXMAB, warrants further investigation and advancement to a frontline phase 3 study.

“This is in a disease that has not seen the approval of any new drugs in the frontline setting for high-risk MDS for almost 20 years outside of an oral formulation of decitabine, so [it is] certainly an area of significant unmet need,” Dr. Zeidan highlighted.