Personalized Timing for Allogeneic Stem-Cell Transplantation in Hematologic Neoplasms: A Target Trial Emulation Approach Using Multistate Modeling and Microsimulation

JCO Clinical Cancer Informatics, vol. 8, pp. e2300205

Abstract

PURPOSE: Decision about the optimal timing of a treatment procedure in patients with hematologic neoplasms is critical, especially for cellular therapies (most including allogeneic hematopoietic stem-cell transplantation [HSCT]). In the absence of evidence from randomized trials, real-world observational data become beneficial to study the effect of the treatment timing. In this study, a framework to estimate the expected outcome after an intervention in a time-to-event scenario is developed, with the aim of optimizing the timing in a personalized manner. METHODS: Retrospective real-world data are leveraged to emulate a target trial for treatment timing using multistate modeling and microsimulation. This case study focuses on myelodysplastic syndromes, serving as a prototype for rare cancers characterized by a heterogeneous clinical course and complex genomic background. A cohort of 7,118 patients treated according to conventional available treatments/evidence across Europe and United States is analyzed. The primary clinical objective is to determine the ideal timing for HSCT, the only curative option for these patients. RESULTS: This analysis enabled us to identify the most appropriate time frames for HSCT on the basis of each patient's unique profile, defined by a combination relevant patients' characteristics. CONCLUSION: The developed methodology offers a structured framework to address a relevant clinical issue in the field of hematology. It makes several valuable contributions: (1) novel insights into how to develop decision models to identify the most favorable HSCT timing, (2) evidence to inform clinical decisions in a real-world context, and (3) the incorporation of complex information into decision making. This framework can be applied to provide medical insights for clinical issues that cannot be adequately addressed through randomized clinical trials.

Authors 14

1. Caterina Gregorio corresponding

   University of Trieste · Stockholm University · Karolinska Institutet · Politecnico di Milano

   Affiliation as printed

   Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden

   Biostatistics Unit, Department of Medical Sciences, University of Trieste, Trieste, Italy

   MOX—Modelling and Scientific Computing Laboratory, Politecnico di Milano, Department of Mathematics, Milan, Italy

   MOX-Modelling and Scientific Computing Laboratory, Politecnico di Milano, Department of Mathematics, Milan, Italy

2. Marta Spreafico Aachen Mathematical Institute

   Leiden University

   Affiliation as printed

   Mathematical Institute, Leiden University, Leiden, the Netherlands

3. Saverio D’Amico
   Affiliation as printed

   Humanitas Clinical and Research Center—IRCCS, Milan, Italy

   Humanitas Clinical and Research Center-IRCCS, Milan, Italy

4. Elisabetta Sauta
   Affiliation as printed

   Humanitas Clinical and Research Center—IRCCS, Milan, Italy

   Humanitas Clinical and Research Center-IRCCS, Milan, Italy

5. Gianluca Asti
   Affiliation as printed

   Humanitas Clinical and Research Center—IRCCS, Milan, Italy

   Humanitas Clinical and Research Center-IRCCS, Milan, Italy

6. Luca Lanino

   Humanitas University

   Affiliation as printed

   Department of Biomedical Sciences, Humanitas University, Milan, Italy

   Humanitas Clinical and Research Center—IRCCS, Milan, Italy

   Humanitas Clinical and Research Center-IRCCS, Milan, Italy

7. Cristina Astrid Tentori

   Humanitas University

   Affiliation as printed

   Department of Biomedical Sciences, Humanitas University, Milan, Italy

   Humanitas Clinical and Research Center—IRCCS, Milan, Italy

   Humanitas Clinical and Research Center-IRCCS, Milan, Italy

8. Uwe Platzbecker

   University Hospital Leipzig

   Affiliation as printed

   Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany

9. Torsten Haferlach

   Munich Leukemia Laboratory (Germany)

   Affiliation as printed

   MLL Munich Leukemia Laboratory, Munich, Germany

10. María Díez‐Campelo

    Complejo Hospitalario de Salamanca

    Affiliation as printed

    Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain

11. Pierre Fenaux

    Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis · Université Paris Diderot

    Affiliation as printed

    Department of Hematology and Bone Marrow Transplantation, Hôpital Saint-Louis/Assistance Publique-Hôpitaux de Paris (AP-HP)/University Paris 7, Paris, France

12. Rami S. Komrokji

    Moffitt Cancer Center

    Affiliation as printed

    Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL

13. Matteo Giovanni Della Porta

    Humanitas University

    Affiliation as printed

    Department of Biomedical Sciences, Humanitas University, Milan, Italy

    Humanitas Clinical and Research Center—IRCCS, Milan, Italy

    Humanitas Clinical and Research Center-IRCCS, Milan, Italy

14. Francesca Ieva

    Human Technopole · Politecnico di Milano

    Affiliation as printed

    HDS, Health Data Science Center, Human Technopole, Milan, Italy

    MOX—Modelling and Scientific Computing Laboratory, Politecnico di Milano, Department of Mathematics, Milan, Italy

    MOX-Modelling and Scientific Computing Laboratory, Politecnico di Milano, Department of Mathematics, Milan, Italy