Fitness-for-Use Assessment across Four Data Sources for Real-World Safety and Effectiveness Studies of CAR-T cell therapies

Study type

• Study topic:
  Human medicinal product
• Study type:
  Not applicable
• Scope of the study:
  Feasibility analysis
• If ‘Not applicable’, further details on the study type:
  This is a fitness‑for‑use, non‑interventional methodological assessment designed to evaluate whether four real‑world data sources (NCRAS & HES, US Flatiron Health Research Database, SNDS and DESCAR‑T) are suitable for conducting regulatory‑relevant CAR-T cell therapy research. It does not generate clinical evidence but systematically assesses each data source’s ability to support these theoretical study scenarios.
• Data collection methods:
  Secondary use of data

Study drug and medical condition

• Medicinal product name:
  ABECMA

  BREYANZI

  CARVYKTI

  KYMRIAH

  TECARTUS

  YESCARTA
• Anatomical Therapeutic Chemical (ATC) code:
  (L01XL07) idecabtagene vicleucel

  idecabtagene vicleucel

  (L01XL08) lisocabtagene maraleucel

  lisocabtagene maraleucel

  (L01XL05) ciltacabtagene autoleucel

  ciltacabtagene autoleucel

  (L01XL04) tisagenlecleucel

  tisagenlecleucel

  (L01XL06) brexucabtagene autoleucel

  brexucabtagene autoleucel

  (L01XL03) axicabtagene ciloleucel

  axicabtagene ciloleucel

Population studied

• Short description of the study population:
  For each theoretical scenario, a series of inclusion and exclusion criteria were specified and the extent to which these eligibility criteria might be implemented in each data source was evaluated as part of the fitness-for-purpose assessment. The inclusion and exclusion criteria have been formulated to align with the CARTITUDE-1 and CARTITUDE-4 trials, where applicable. A brief illustrative overview of the eligibility criteria for each theoretical scenario is provided below. ; ; Theoretical Scenario 1 ; The study population included patients who received at least one dose of a CAR-T cell therapy during the indexing period (23 August 2018 to 31 December 2024) and who had 12 months data source history. Patients were excluded if they had evidence of any of the safety outcomes of interest or were enroled in a clinical trial in the 12 months prior to index date. ; ; Theoretical Scenario 2; The study population included adults with multiple myeloma (MM), with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, who received 3 or more previous LOT or were double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), and had received a PI, IMiD, and an anti-CD38 antibody. Patients who met the above criteria and initiated a standard of care MM treatment during the indexing period (01 January 2018 to 31 December 2023) were included. Patients were excluded if they received CAR-T cell therapy or an agent targeting B-cell maturation antigen prior to index date. ; ; Theoretical Scenario 3; The study population was adults with MM, with an ECOG performance status score of 0 or 1, who were lenalidomide-refractory and who had received one to three LOT including a PI or an IMiD and who initiated treatment with cilta-cel (treatment arm) or pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (comparison arm) during the indexing period (28 February 2022 to 31 December 2023). Patients were excluded if they received CAR-T cell therapy or an agent targeting BCMA prior to index date.; ;
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Study design details

• Study design:
  This is a fitness-for-use assessment to test the feasibility of implementing the three theoretical scenarios in NCRAS & HES, US Flatiron Health Research Database, SNDS and DESCAR-T data sources. A retrospective, observational cohort design was used as a template for each theoretical scenario.;
• Main study objective:
  To evaluate the fitness-for-purpose of NCRAS & HES, US Flatiron Health Research Database and Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells (DESCAR-T) data sources to address the following regulatory-relevant theoretical scenarios: ; ; 1. To estimate the incidence rates of five safety outcomes (neurotoxicity, CRS, neutropenia, infections, second primary malignancies) among patients treated with CAR-T cell therapy; 2. To develop an external control arm for CARTITUDE-1, a single-arm phase 1b/2 trial (NCT03548207) to assess the effectiveness of cilta-cel among adult patients with relapsed-refractory MM; 3. To emulate the CARTITUDE-4 (NCT04181827) clinical trial to compare the effectiveness of cilta-cel to standard of care among adult patients with lenalidomide-refractory MM who had received 1-3 prior LOT (CARTITUDE-4 clinical trial emulation).;
• Setting:
  The study is conducted within four real‑world data sources, NCRAS & HES in England, US Flatiron Health Research Database in the United States, and SNDS and DESCAR‑T in France, each capturing oncology patients from 2018 onwards, when CAR‑T therapies became available.
• Interventions:
  This project does not involve any patient level intervention and is neither a clinical trial nor a non interventional study; rather, it is a non interventional methodological assessment conducted solely to evaluate the fitness for purpose of selected real world data sources for potential future regulatory studies on CAR T cell therapies.
• Outcomes:
  The study assessed whether each data source could accurately capture key safety (e.g., cytokine release syndrome, secondary malignancies) and effectiveness (e.g., progression, response, overall survival) endpoints.
• Data analysis plan:
  Aligning with the approach recommended in the European Medicine Agency (EMA) “Data Quality Framework for European Union (EU) medicines: Application to Real-World data”, a series of research question-specific metrics for each dimension of data quality (extensiveness, coherence, reliability, relevance and timeliness) were evaluated as part of the fitness-for-purpose assessment of each data source for each theoretical scenario.