Abstract 2064: Unveiling the correlation between gemtuzumab-ozogamicin efficacy and CD33+ expression in AML primary samples using the novel AML vitroscreen

Abstract Acute myeloid leukemia (AML) poses a significant therapeutic challenge, with a rising incidence in recent times. This clonal hematopoietic disorder of progenitor and stem cells exhibits aggressive behavior, and despite initial remission, recurrence is common1. The conventional shift from chemotherapy to monoclonal antibodies and antibody-drug conjugates (ADCs) has been hindered by the absence of AML-specific antigens. Notably, CD33, expressed strongly in 80-90% of AML cells, has become a target for gemtuzumab-ozogamicin (Mylotarg), the sole FDA approved ADC for AML treatment2. While advancements in understanding AML molecular mechanisms have influenced clinical approaches, the lack of clinically representative models hinders therapeutic progress. Existing models, both in vivo and ex vivo, struggle to capture the heterogeneity and complexity of AML3. Addressing this, we present our proprietary assay, Champions AML VitroScreen®4, designed for testing therapeutic candidates in primary AML samples. Our diverse bank of deeply characterized AML samples encompasses multiple subtypes, allowing evaluation of therapeutic responses through cell viability, proliferation, and clonal composition analyses. To validate our novel assay, we employed the VitroScreen platform to test Mylotarg across various AML subtypes, considering CD33 expression levels. By assessing more than 20 AML models, we determined the IC50 for Mylotarg and observed dose-dependent responses, where sensitivity to the drugh correlated with CD33 expression. Through multiple endpoints, including viability, proliferation, apoptosis, and phenotyping, we categorized primary AML models as responders, low responders, or resistant, establishing a strong positive correlation between Mylotarg sensitivity and CD33 expression. Our innovative approach, utilizing deeply characterized AML patient samples in the AML VitroScreen® platform, facilitates high-throughput drug testing. This system, serving as an ideal clinical translational setting in preclinical research, holds promise for developing tailored therapeutic strategies. Ultimately, this approach could significantly impact patient outcomes by offering improved strategies for both primary and recurrent AML cases. Citation Format: Mara Gilardi, Garima Kaushik, Brandon Walling, Paolo Schiavini, Stefano Cairo, Marianna Zipeto. Unveiling the correlation between gemtuzumab-ozogamicin efficacy and CD33+ expression in AML primary samples using the novel AML vitroscreen abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2064.