Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

  • Nico Gagelmann (Shared first author)
  • Danai Dima (Shared first author)
  • Maximilian Merz (Shared first author)
  • Hamza Hashmi (Shared first author)
  • Nausheen Ahmed
  • Natalia Tovar
  • Aina Oliver-Caldés
  • Friedrich Stölzel
  • Kristin Rathje
  • Luise Fischer
  • Patrick Born
  • Lisa Schäfer
  • Anca-Maria Albici
  • Natalie Schub
  • Shlomit Kfir-Erenfeld
  • Miri Assayag
  • Nathalie Asherie
  • Gerald Georg Wulf
  • Soraya Kharboutli
  • Fabian Müller
  • Leyla Shune
  • James A Davis
  • Faiz Anwer
  • Vladan Vucinic
  • Uwe Platzbecker
  • Francis Ayuk
  • Nicolaus Kröger
  • Jack Khouri
  • Carmelo Gurnari
  • Joseph McGuirk
  • Polina Stepensky (Shared last author)
  • Al-Ola Abdallah (Shared last author)
  • Carlos Fernández de Larrea (Shared last author)

Abstract

PURPOSE: Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T.

PATIENTS AND METHODS: This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti-B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133). Independent predictors of relapse/progression built a simple prediction model (Myeloma CAR-T Relapse [MyCARe] model) in the training cohort (Europe), which was externally validated (US cohort) and tested within patient- and treatment-specific subgroups.

RESULTS: The overall response rate was 87% and comparable between both cohorts, and complete responses were seen in 48% (Europe) and 49% (the United States). The median time to relapse was 5 months, and early relapse <5 months from infusion showed poor survival across cohorts, with the 12-month overall survival of 30% (Europe) and 14% (the United States). The presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. Each factor received one point, forming the three-tiered MyCARe model: scores 0-1 (low risk), scores 2-3 (intermediate risk), and a score of 4 (high risk). The MyCARe model was significantly associated with distinct 5-month incidence of relapse/progression (P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. The model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups.

CONCLUSION: Outcomes of patients with RRMM after CAR-T are comparable between Europe and the United States. The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups.

Bibliographical data

Original languageEnglish
ISSN0732-183X
DOIs
Publication statusPublished - 10.05.2024
PubMed 38358946