Abstract 5567: Targeted immunotherapies in multiple myeloma: focus on flow cytometry markers and therapeutic implications

Abstract Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of malignant plasma cells. Despite advancements, MM remains one of the most prevalent hematological malignancies with over 30, 000 new cases annually. However, the emergence of immunotherapy through the targeting of specific cell surface proteins has transformed the treatment landscape for MM and highlights the need for the identification and evaluation of unique immunotherapy targets, particularly in relapsed or refractory cases. Drugs to CD38 (Daratumumab & Isatuximab) and SLAMF7 (Elotuzumab) have demonstrated the potency of these therapies, particularly when utilized in combinations. Flow cytometry plays a vital role in diagnosing MM and in evaluating minimal residual disease (MRD), however, it also functions as an excellent method through which to interrogate the expression of unique markers and subpopulations. Here we have utilized Champion Oncology’s cryopreserved primary MM patient samples derived from bone marrow aspirates to generate a platform for the interrogation of novel biomarkers utilizing flow cytometry, sequencing, and ex vivo analysis. We have performed cellular deconvolution on these models to sort and interrogate populations based on numerous factors including tumor type, treatment history, and diagnosis. This provides rapid mechanisms to identify populations of interest for unique signatures. These identified targets may then be utilized via flow cytometry to characterize models with an adaptable “drop-in” panel which facilitates the addition of multiple novel targets for rapid screening. These data can be further stratified utilizing the canonical MM markers to evaluate the expression within subpopulations and how these subpopulations evolve throughout treatment. Finally, those models that have been identified can be utilized in ex vivo assays. Using six unique MM models stratified into refractory, naive, and relapsed, we evaluated the ex vivo response to current standard of care (SOC) treatments allowing for drug sensitivity screening and the evaluation of novel target responses. Collectively, these data demonstrate a robust method for rapid identification and evaluation of unique MM targets. Citation Format: Haoting Hsu, Elena Bruni, Claudia Carenza, Karolina Pilipow, Paolo Schiavini, Christine Baer, Gilad Silberberg, BanuPriya Sridharan, Mara Gilardi, Stefano Cairo, Brandon Walling. Targeted immunotherapies in multiple myeloma: focus on flow cytometry markers and therapeutic implications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5567.