Jerina Hoxha
3.7.25
New article highlights CERTAINTY’s approach to advancing personalised treatment
A new Focus article in The Lancet Haematology showcases CERTAINTY's pioneering efforts to develop a virtual twin (VT) that can transform personalised treatment strategies for patients receiving CAR T cell therapy in relapsed/refractory multiple myeloma (RRMM). This work outlines a comprehensive framework combining multiscale computational models with real-world patient data to improve treatment planning, safety, and accessibility.
Background
Multiple myeloma is an incurable blood cancer characterised by clonal proliferation of plasma cells and significant disease heterogeneity. While CAR T cell therapies directed against B-cell maturation antigen (BCMA), such as Ide-cel and Cilta-cel, have revolutionised treatment, their implementation remains complex and costly. Patients face logistical challenges in manufacturing, risks of severe toxicities like cytokine release syndrome and neurotoxicity, and the possibility of treatment resistance.
The concept of a VT, an advanced form of digital twin integrating patient-specific data and predictive modelling, offers an innovative path towards overcoming these challenges. CERTAINTY aims to develop a VT that captures the treatment journey, from the indication for CAR T to long-term follow-up after CAR T treatment.
Key Points
The article details how the CERTAINTY VT will:
Incorporate Multiscale Data: Integrate molecular, cellular, tissue, and organ-level information, combining longitudinal clinical datasets and de-novo single-cell multi-omics data.
Leverage Diverse Modelling Approaches: Employ mechanistic models, stochastic simulations, artificial intelligence, and computational structural biology to replicate and predict patient responses before, during, and after CAR T cell therapy.
Support Personalised Decision-Making: Enable clinicians to compare an individual patient’s virtual profile against historical cases to optimise treatment timing, bridging therapies, and manufacturing workflows.
Enhance Safety and Quality Control: Predict early signs of toxicities and identify potential bottlenecks or quality issues in decentralised manufacturing processes.
Facilitate Co-Creation and Regulatory Readiness: Engage clinicians, patients, regulators, and researchers in designing VT modules and interfaces, with plans to evaluate performance in tumour board decision-making scenarios.
Conclusions
CERTAINTY’s VT prototype represents a significant step towards making personalised CAR T cell therapy safer, more efficient, and more broadly accessible. By integrating cutting-edge computational models with comprehensive patient data, the project is laying the groundwork for a decision support system that can help clinicians anticipate complications, adjust treatment plans, and ultimately improve outcomes for patients with multiple myeloma.
Access the Article
The full article is available online through The Lancet Haematology: Digital Haematology: http://doi.org/10.1016/S2352-3026(25)00170-X