Abstract 184: Multiple Myeloma 3D model: A platform for testing drug effects on myeloma in conjunction with the bone marrow niche
Authors: Rashad Hanadi M. , Insuasti Giovanni , Almeida-Porada Graca , Rodriguez Cesar 
Published: June 2023

Background: Multiple myeloma is a cancer that remains mostly incurable despite of the wide array of treatment options. In part, this may be due to its ability to develop resistance to therapy with time. To evaluate key aspects of the disease such as the protective effects of the tumor niche, the immune repertoire that could influence immunotherapies and the ability to study primary tumor cells, developing a new platform is necessary. In order to overcome the obstacles of growing primary myeloma cells and having a model that better replicates the tumor microenvironment, we used a 3D organoid model with patient-derived cells to evaluate different conditions to observe how current therapies affects cancer cells and the tumor niche in which they live.

Methods: We used a 3D organoid model using patient bone marrow aspirates containing myeloma cells and stroma in a Matrigel scaffold and incubated over 21 days with partial media change containing key growth factors found in the bone marrow space to maintain cells alive. Established agents used to treat myeloma were used to expose the cultures and then monitored at different timepoints to study its immediate and delayed effect in the tumor cells, immune repertoire, and stroma. Bortezomib, Lenalidomide, Selinexor, and Dexamethasone, which are commonly used to treat myeloma patients and influence the immune compartment, were used at different concentrations. ATP, alamar blue, histology, and flow cytometry were performed at key timepoints of the experiment.

Results: H&E sections demonstrated hematopoietic elements with good cellular preservation suggesting that the model may be a functional way to recapitulate the tumor environment. Patient-derived Multiple Myeloma organoids treated with Bortezomib 10nM and Selinexor 10uM and 30uM showed significant inhibition in viability compared to control. Lenalidomide 100 uM had variable effect in viability between organoids. Flow Cytometry analysis captured the immunomodulatory effect of Lenalidomide on the immune cells.

Conclusions: The 3D organoid model was successful at maintaining viability for 21 days and having a heterogeneous representation of the tumor niche when using bone marrow aspirates of myeloma patients. The experiments performed allowed us to explore not just the effect of drugs on myeloma cells, but we can see the impact they have on the other cells in the bone marrow niche. A unique interest in the ability to evaluate changes in the immune compartment may help better understand immunotherapy and optimize personalized medicine by helping select the most effective treatments for a particular patient.

Citation Format: Hanadi M. Rashad, Giovanni Insuasti, Graca Almeida-Porada, Cesar Rodriguez. Multiple Myeloma 3D model: A platform for testing drug effects on myeloma in conjunction with the bone marrow niche [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 184.