The study that was presented at EHA is about patients with either relapsed/refractory myelodysplasia or high-risk untreated myelodysplasia using a novel drug, using a Clever-1 antibody which is a novel macrophage immune checkpoint inhibitor, together with azacitidine. Basically, the Clever-1 antibody converts the mechanism of action, it converts anti-tumorigenic macrophages to pro-inflammatory and activates a T-cell response. It also may have an effect on blast cell energy production as it has an effect on oxidative phosphorylation. It essentially has a triple mechanism of action.

What is the study design?

The study design was basically, again, two cohorts of patients, one with frontline MDS and one that had high or very high risk disease. The second group of patients were patients with relapsed/refractory myelodysplasia and they all had failed a prior hypomethylating agent. The design was basically a phase I/phase II design – once the optimum dose of bexmarilimab was found it then moved to the phase II part of the study where two doses of bexmarilimab was tested, either the 6mg/kg dose or the 3mg/kg dose.

What were the results of this study?

In frontline high-risk MDS patients there were 21 patients treated. If you classify them by the latest 2023 IWG classification, the overall response rate was 55% and the CCR rate was 50%. Of these patients, 20% had a complete response, 15% CREQ and 15% CRL. 45% of patients did not respond to the treatment.

For the patients with relapsed/refractory MDS, again by the latest IWG 2023 classification, the overall response rate was 47% and complete CR rate was 16%. The median overall survival for the relapsed/refractory group of patients was estimated at about 13.4 months and the 95% confidence interval is 4.8 months to being not reached.

What is the clinical significance of these results?

So far for myelodysplasia patients failing hypomethylating agents there is no effective therapy. The study showed a 63% overall response rate by IWG 2006 in this group of patients. In the frontline setting for intermediate and high-risk patients by the 2006 criteria there was an 85% overall response rate. Based on these encouraging data a phase III randomised study is being planned comparing azacitidine, which is the standard of therapy, to azacitidine plus bexmarilimab.

Is there anything else you would like to add?

Bexmarilimab was well tolerated in this group of patients. The safety data remains favourable – 13% of patients discontinued treatment due to treatment emergent adverse events. Only one patient discontinued bexmarilimab due to encephalopathy. There were three grade 5 treatment emergent events but none of these were attributed to bexmarilimab.

The most common bexmarilimab-related AEs were white cell count decreased in 11.3% of patients, fatigue in 7.6% of patients and neutrophil count decreased in 7.6% of patients. So overall the drug is very well tolerated and the bexmarilimab is given on a weekly