Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience

Haematologica. 2024 May 1;109(5):1514-1524. doi: 10.3324/haematol.2023.283888.

Abstract

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤3 months after CAR T-cell infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤3 months of infusion (P<0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (P<0.001; median PFS for ≥3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T-cell therapy who may benefit from specific interventions pre and post CAR T-cell therpy to improve outcomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD19 / immunology
  • Antigens, CD19 / therapeutic use
  • B-Cell Maturation Antigen / immunology
  • Biological Products / administration & dosage
  • Biological Products / therapeutic use
  • Disease Progression*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Male
  • Middle Aged
  • Multiple Myeloma* / immunology
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / therapy
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / therapeutic use
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / therapeutic use
  • Recurrence
  • Risk Factors
  • Treatment Outcome
  • United States / epidemiology

Substances

  • idecabtagene vicleucel
  • Biological Products
  • B-Cell Maturation Antigen
  • Antigens, CD19
  • Recombinant Fusion Proteins
  • Receptors, Chimeric Antigen