Ja Rotterdamin Abstract on saatavilla. Tuosta sitten Zeidan lähtee kertomaan.
Background and Aims
Treatment of higher risk (HR) myelodysplastic syndrome (MDS) with primary refractory disease or relapse after frontline treatment (r/r MDS) with hypomethylating agent (HMA), represents a high unmet medical need. Phase 1/2 BEXMAB study (NCT05428969) evaluates safety, tolerability, and preliminary efficacy of bexmarilimab, a monoclonal antibody blocking Common lymphatic and vascular endothelial receptor-1 (Clever-1), plus azacitidine in myeloid malignancies including r/r MDS. Through Clever-1 inhibition, bexmarilimab alters the bone marrow (BM) microenvironment and the fitness of malignant blasts, thereby enhancing the effectiveness of azacitidine in patients with r/r MDS.
Methods
As of 25 November 2024, 20 patients with r/r MDS were enrolled in the ongoing Phase 1/2 BEXMAB study after HMA failure. All patients had IPSS-R >3.5 and 9/20 were TP53 mutated. Bexmarilimab was administrated weekly in 28-day cycles, at 1, 3, and 6 mg/kg, in combination with a standard regimen of azacitidine.
Results
Altogether, 184 treatment-emergent adverse events (TEAE) were reported, of which 25 (13.6%) were considered to be bexmarilimab-related (all Gr 1-2). The objective response rate (ORR; CR+mCR+PR+HI) was 80% (16/20) in r/r MDS patients per IWG2006 criteria. Per IWG2023 criteria the ORR (CR+CRequivalent+CRh+CRL+PR+HI) was 65% (13/20). Complete remission (CR) rate was 5% (1/20) per IWG2006 criteria and CR+CRL rate was 20% (4/20) per IWG2023 criteria. Further updated efficacy parameters including duration of treatment and transfusion independence, will be reported at the meeting, together with updated BM Clever-1 expression biomarker data.
Conclusions
Bexmarilimab plus azacitidine is well tolerated and results in promising clinical efficacy in r/r MDS patients after HMA failure.