Abstract 3412: Patient-derived MicroOrganoSpheres (MOS) enable precision clinical decision-making for multiple myeloma patients

Abstract

Abstract There are many equipoised multiple myeloma (MM) treatments and nearly all relapse patients undergo cycles of treatment, response, and relapse management. Selecting the right agents and right drug combination is thus of critical importance and an area of unmet need. We currently lack patient-derived MM models that can enable functional precision medicine to help real-time clinical decision-making to guide individual patient treatment. We have created a method to grow MM patient avatars in MicroOrganoSheres (MOS), microscale droplet ECM that sustain the original tumor microenvironment (TME) including both stromal and immune compartments. MOS enable reliable testing of available drug combinations and experimental drugs within 10 days of bone marrow (BM) biopsy, making it feasible to guide treatment decisions in the clinic. In the current study, BMB-derived MM MOS were generated via droplet microfluidics and cultured in vitro, followed by live MOS staining and flow cytometry. Drug screen was performed on MOS with FDA-approved single agents and combinations. Responses of tumorspheres within MOS to drug treatments were quantified by AI-based live imaging algorithms to generate robust drug response curves and derive IC50 and EC50. We successfully established from all 6 MM BM biopsies, MOS conserved CD138/CD38 tumor cell, stromal (e.g., osteoblast) cells, and all major immune cell populations, including T, NK, B, macrophage, dendritic, and myeloid-derived suppressor cells till at least 11 days after the drug assays were completed. The vast number of MOS generated from a single BM biopsy enabled high-throughput drug screening within 10 days. We tested standard-of-care drugs and their combinations applicable to the patient in 9-dose titrations. Live/dead dye fluorescence signal was obtained after 5 days drug dosing and analyzed using Xilis AI analysis pipeline. We generated MOS drug response curve and IC50s from each biopsy. Drug responses from the first 6 MM patient MOS correlates well with their clinical outcome. Furthermore, this MOS platform enabled us to evaluate experimental therapies currently in Phase I-III clinical trials, which revealed responsive patients and insights into optimal combinations that will further improve efficacy. Based on this groundbreaking study, a clinical trial including 40 patients is starting in a month to further validate the predictability of the MM MOS assay for therapeutic decision-making in the clinic. Citation Format: Rui Xi, Xiaobei Wang, Robert Moseley, Renuka Raman, Ray Zhang, Shaima Jaibbar, Shaun Steele, Shengi Ding, Yubing Kang, Xiling Shen. Patient-derived MicroOrganoSpheres (MOS) enable precision clinical decision-making for multiple myeloma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3412.