Single-Cell Multi-Omics of Peripheral Blood Reveals Tiding and Evolution of Responsive and Resistant Clones upon Daratumumab-Based Treatments in Multiple Myeloma and Plasma Cell Leukemia

Grieb, Nora; Sia, Jaren; Scolnick, Jonathan; Cordes, Shaun; Kloetzer, Christina; Heyn, Simone; Strenge, Julia; Tumewu, Theresa; Gerhardt, Kristen; Nenoff, Kolja; Kubasch, Anne Sophie; Wang, Song Yau; Bach, Enrica; Jentzsch, Madlen; Franke, Georg‐Nikolaus; Schwind, Sebastian; Metzeler, Klaus H.; Herling, Marco; Vučinić, Vladan; Platzbecker, Uwe; Merz, Maximilian

doi:10.1182/blood-2022-166241

Cited by 1 publication

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“…Genomic analyses of tissue samples from myeloma patients have shown that MM represents a spectrum of hematological entities with extensive tumor heterogeneity. Multiple layers of this complexity have already been studied in multi-omics settings, including inter-and intra-patient diversity, disease state, relapse status, treatment response and spatial heterogeneity in bone disease (54)(55)(56)(57)(58)(59)(60). Results comprehensively highlight the need for profiling clonal heterogeneity and molecular processes associated with MM at each development stage (61).…”

Section: Discussionmentioning

confidence: 99%

A digital twin model for evidence-based clinical decision support in multiple myeloma treatment

Grieb,

Schmierer,

Kim

et al. 2023

Front. Digit. Health

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The treatment landscape for multiple myeloma (MM) has experienced substantial progress over the last decade. Despite the efficacy of new substances, patient responses tend to still be highly unpredictable. With increasing cognitive burden that is introduced through a complex and evolving treatment landscape, data-driven assistance tools are becoming more and more popular. Model-based approaches, such as digital twins (DT), enable simulation of probable responses to a set of input parameters based on retrospective observations. In the context of treatment decision-support, those mechanisms serve the goal to predict therapeutic outcomes to distinguish a favorable option from a potential failure. In the present work, we propose a similarity-based multiple myeloma digital twin (MMDT) that emphasizes explainability and interpretability in treatment outcome evaluation. We've conducted a requirement specification process using scientific literature from the medical and methodological domains to derive an architectural blueprint for the design and implementation of the MMDT. In a subsequent stage, we've implemented a four-layer concept where for each layer, we describe the utilized implementation procedure and interfaces to the surrounding DT environment. We further specify our solutions regarding the adoption of multi-line treatment strategies, the integration of external evidence and knowledge, as well as mechanisms to enable transparency in the data processing logic. Furthermore, we define an initial evaluation scenario in the context of patient characterization and treatment outcome simulation as an exemplary use case for our MMDT. Our derived MMDT instance is defined by 475 unique entities connected through 438 edges to form a MM knowledge graph. Using the MMRF CoMMpass real-world evidence database and a sample MM case, we processed a complete outcome assessment. The output shows a valid selection of potential treatment strategies for the integrated medical case and highlights the potential of the MMDT to be used for such applications. DT models face significant challenges in development, including availability of clinical data to algorithmically derive clinical decision support, as well as trustworthiness of the evaluated treatment options. We propose a collaborative approach that mitigates the regulatory and ethical concerns that are broadly discussed when automated decision-making tools are to be included into clinical routine.

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