[00:11] Landscape of MDS and AML
[03:45] Higher-risk MDS: treatments challenges after Azacitidine failure
[ 07:20 ] Why BCL inhibitions in MDS and the promising new BCLi- Mesutoclax
[ 09:54 ] The TN-MDS Data: 100% ORR and 90% composite CR
[12:49] Bridging to AML: the scientific case for Mesutoclax over Venetoclax
[14:06 ] TN-AML: composite CR rate of more than 80%
[15:49 ] R/R AML: after Venetoclax failure: Mesutoclax shows promising activity in R/R AML
[17:16 ] Favorable Safety: No DLTs, Zero Early Mortality
[18:53] Promising future for patients in MDS and AML
High-risk myelodysplastic syndromes and acute myeloid leukemia remain areas of significant unmet need, particularly for older patients who cannot tolerate intensive therapy. In this episode of The Top Line, Yale hematologic malignancies expert Dr. Amer Zeidan discusses why treatment progress in high-risk MDS has stalled and why emerging BCL2 inhibitors may mark a turning point.
The conversation focuses on new ASCO 2026 data for mesutoclax, a novel oral BCL2 inhibitor studied in combination with azacitidine, which demonstrated favorable safety and efficacy in the treatment of both MDS and AML.
Dr. Zeidan said that mesutoclax is an oral novel BCL2 inhibitor that appears to be more potent than venetoclax, and he also mentioned mesutoclax looks quite promising. In treatment-naive high-risk MDS, the regimen produced a 100% objective response rate with CR rate of 40% per IWG 2006 criteria and a 90% composite complete response with CR in 60% per IWG 2023 criteria, far exceeding historical benchmarks. In AML, mesutoclax also showed high response rates and a favorable safety profile, with over 80% composite CR, and with potent activity in TP53 mutant, as well as zero death within 30 or 60 days and rapid cytopenia recovery.
Dr. Zeidan explains how mesutoclax's pharmacologic design may address limitations seen with venetoclax, including drug-drug interactions and prolonged cytopenias. While longer follow-up and randomized data are still needed, the early signals suggest meaningful potential in both frontline and relapsed settings.
The opinions expressed in this podcast summary article are solely those of Dr. Zeidan and do not necessarily reflect the views or opinions of his employer.