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Cancer

Germline Genetic Aberrations Predict Toxicity and Efficacy in B-Cell Lymphoma Patients Treated with CAR T-Cell Therapy

Strategic Insights

— 1 min read

Recent research conducted by investigators at the University of Texas MD Anderson Cancer Center has shed new light on the role of germline genetic aberrations in predicting toxicity and efficacy in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy (CART). The study, published in the Journal for ImmunoTherapy of Cancer, analyzed genetic data from 170 patients and identified several genetic risk factors associated with increased risk of cytokine release syndrome and cytopenia.

Key Takeaways:

  • Germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma treated with CART.
  • Increasing PRS for monocyte count was associated with increased risk of cytokine release syndrome of any grade (OR 2.49, 95% CI 1.18 to 5.25, p=0.016).
  • Genetically predicted interleukin (IL)-1Ra and (IL)-27 levels were decreased (p=0.002) and increased (p=0.012) in patients with G3-4 day 30 cytopenia, respectively.
  • The latter was also associated with variation in the hemophagocytic lymphohistiocytosis-related gene RAB27A (p=0.041).
  • Genome-wide significant (p<5 × 10-8) associations were observed between PRS for monocyte count and cytokine release syndrome (p=0.008).
  • Elucidating such intrinsic determinants may help improve patient selection and develop strategies to enhance the therapeutic index of CART.
  • The study was funded by the National Institutes of Health and the University of Texas Md Anderson Cancer Center.
  • Additional authors for the research include Sattva S Neelapu, Partow Kebriaei, Sherry Adkins, Michelle A T Hildebrandt, Anath C Lionel, Jared Henderson, Christopher Flowers, Paolo Strati, Amanda Brandt, Jason R Westin, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed.

Statistics:

  • 170 patients with large B-cell lymphoma were included in the study.
  • The analysis identified several genetic risk factors associated with increased risk of cytokine release syndrome and cytopenia.
  • Patients with increasing PRS for monocyte count were at increased risk of cytokine release syndrome of any grade (OR 2.49, 95% CI 1.18 to 5.25, p=0.016).
  • Genetically predicted interleukin (IL)-1Ra and (IL)-27 levels were decreased (p=0.002) and increased (p=0.012) in patients with G3-4 day 30 cytopenia, respectively.
  • The study found a genome-wide significant (p<5 × 10-8) association between PRS for monocyte count and cytokine release syndrome (p=0.008).

Sources:

  • Journal for ImmunoTherapy of Cancer, 2025,13(10).
  • National Institutes of Health.
  • University of Texas Md Anderson Cancer Center.

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