Abstract 330: Reconstructed Bone (r-Bone): A patient-derived 3D culture platform for prediction of clinical outcomes in multiple myeloma

Abstract

Abstract Multiple myeloma (MM), an incurable cancer of the bone marrow plasma cells, is a second most common hematological malignancy. While considerable progress has been made towards treatment of MM, the 5-year survival rate continues to hover around 50%. In this study, we aimed to evaluate the capacity of the Reconstructed Bone (r-Bone) model to predict clinical outcomes in patients with multiple myeloma. The r-Bone system incorporates cellular (hematopoietic and stromal) and extracellular (extracellular matrix and secretory factors) components, supports long-term survival (>30 days) and proliferation, and maintains cellular heterogeneity of the primary human bone marrow. The 1-to-1 reconstruction of the bone marrow architecture established by the r-Bone platform provides an ideal in vitro system to evaluate the efficacy of anti-myeloma agents to select those with highest probability of clinical success. Bone marrow aspirates collected from 21 patients with multiple myeloma were processed and set-up in r-Bone cultures. To establish the correct bone marrow architechture, cultures where grown for 5 days, after which the cells were treated according to the clinical regimen selected by the treating physician based on the orginal bone marrow aspirate. Subsequently, cells were isolated from the r-Bone and processed for flow cytometry. Plasma and non-plasma cell populations were evaluated post-treatment and the extent of cell death was correlated with the observed clinical response. r-Bone cultures correctly predicted the outcome of 19 out of 21 cases with 8 true positivies, 11 true negatives, and 2 false positives. This data demonstrate that the r-Bone system could be used for pipeline attrition management to select drug candidates with the highest probability of clinical success and can be developed into a prognostic tool for the selection of treatment regimen for patients with multiple myeloma. Citation Format: Julia Kirshner, Amrita Kirshnan, Nitya Nathwani, Myo Htut, Michael Rosenzweig, Chatchada Karanes, Sahebi Firoozeh, Steven Rosen. Reconstructed Bone (r-Bone): A patient-derived 3D culture platform for prediction of clinical outcomes in multiple myeloma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 330.