Author Login

Correspondence to Author: Katj Sepel,Lynn Bennger,Ulke Bacher and Tomas Pabst. 

Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland.

Abstract: One uncommon subtype of B-cell lymphoma with a high recurrence rate is mantle cell lymphoma (MCL). In patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR-T-cell treatment using tisa-cel, somatic mutations in the PPM1D gene were linked to unfavorable outcomes; this finding may also hold true for patients with mantle cell lymphoma undergoing brexu-cel CAR-T-cell therapy.
Methods: This study assessed the impact of low-frequency PPM1D mutations on the safety and effectiveness of brexu-cel CAR-T-cell treatment in the first 16 r/r MCL patients admitted to Inselspital Bern. We also ascertained the prevalence of PPM1D mutations in the peripheral blood cells of MCL patients prior to CAR-T-cell infusion.
Results: With variable allele frequencies (VAF) ranging from 0.011 to 0.099, low-frequency PPM1D gene mutations were present in 25% of cases. The PPM1D mutant (PPM1Dmut) and PPM1D wild-type (PPM1Dwt) groups' clinical responses were compared, and the median progression-free survival was 1 against 32 months (p = 0.07) and the median overall survival was 1.5 versus 27 months (p = 0.001).
Conclusions:According to our research, individuals with mantle cell lymphoma receiving CAR-T-cell therapy may have worse outcomes if they have low frequency PPM1D gene mutations in their peripheral blood cells.

Citation:

Katj Sepel. In Mantle Cell Lymphoma, Low-Frequency Ppm1d Gene Mutations Linked To Poorer Response To Cd19 Targeted Car-T Cell Therapy. Journal of Advanced Therapeutics 2025.