Changes in T‐cell subsets, preexisting cytopenias and hyperferritinaemia correlate with cytopenias after BCMA targeted CAR T‐cell therapy in relapsed/refractory multiple myeloma: Results from a prospective comprehensive biomarker study

Abstract

SummaryBiomarkers for cytopenias following CAR T‐cell treatment in relapsed/refractory (RR) multiple myeloma (MM) are not completely defined. We prospectively analysed 275 sequential peripheral blood (PB) samples from 58 RRMM patients treated with BCMA‐targeted CAR T cells, and then divided them into three groups: (i) baseline (before leukapheresis), (ii) ≤day+30, and (iii) >day+30 after CAR T‐cell therapy. We evaluated laboratory data and performed flow cytometry to determine the (CAR) T‐cell subsets. Baseline hyperferritinaemia was a risk factor for long‐lasting grade ≥3 anaemia (r = 0.47, p < 0.001) and thrombocytopenia (r = 0.44, p = 0.002) after CAR T‐cell therapy. Low baseline haemoglobin (Hb) and PLT were associated with long‐lasting grade ≥3 anaemia (r = −0.56, p < 0.001) and thrombocytopenia (r = −0.44, p = 0.002) respectively. We observed dynamics of CAR‐negative T‐cell subsets following CAR T‐cell infusion. In the late phase after CAR T‐cell therapy (>day+30), CD4Tn frequency correlated with anaemia (r = 0.41, p = 0.0014) and lymphocytopenia was related to frequencies of CD8+ T cells (r = 0.72, p < 0.001) and CD8Teff (r = 0.64, p < 0.001). CD4Tcm frequency was correlated with leucocytopenia (r = −0.49, p < 0.001). In summary, preexisting cytopenias and hyperferritinaemia indicated long duration of grade ≥3 post‐CAR T‐cell cytopenias. Prolonged cytopenia may be related to immune remodelling with a shift in the CAR‐negative T‐cell subsets following CAR T‐cell therapy.