Changes in T-cell subsets, preexisting cytopenias and hyperferritinaemia correlate with cytopenias after BCMA...

Area of Science:

• Hematology
• Immunotherapy
• Oncology

Background:

• Cytopenias are common complications following CAR T-cell therapy in relapsed/refractory multiple myeloma (RRMM).
• Biomarkers predicting the duration and severity of these cytopenias remain incompletely defined.
• Understanding these biomarkers is crucial for managing patients undergoing CAR T-cell treatment.

Purpose of the Study:

• To identify predictive biomarkers for cytopenias post-CAR T-cell therapy in RRMM patients.
• To investigate the association between baseline laboratory values and T-cell subsets with prolonged cytopenias.
• To explore the role of immune remodelling in the development of persistent cytopenias.

Main Methods:

• Prospective analysis of 275 peripheral blood samples from 58 RRMM patients treated with BCMA-targeted CAR T cells.
• Categorization of samples into baseline, ≤day+30, and >day+30 post-therapy groups.
• Evaluation of laboratory data and flow cytometry to determine CAR T-cell subsets and CAR-negative T-cell dynamics.

Main Results:

• Baseline hyperferritinaemia and low baseline hemoglobin/platelets were significant risk factors for long-lasting grade ≥3 anemia and thrombocytopenia.
• Specific CAR-negative T-cell subsets, including CD4Tn, CD8+ T cells, CD8Teff, and CD4Tcm, showed correlations with anemia, lymphocytopenia, and leukocytopenia in the late phase (>day+30).
• Dynamics in CAR-negative T-cell subsets were observed following CAR T-cell infusion, suggesting a role in immune remodelling.

Conclusions:

• Pre-existing cytopenias and hyperferritinaemia are key indicators of prolonged severe cytopenias after CAR T-cell therapy.
• Immune remodelling, characterized by shifts in CAR-negative T-cell subsets, may underlie persistent cytopenias.
• These findings aid in predicting and potentially managing post-CAR T-cell cytopenias in RRMM.