Abstract
Retrospective studies suggest that chimeric antigen receptor T-cell (CAR T) therapy may lead to cardiac injury, but this has not been assessed systematically or prospectively. In this prospective study of 40 patients who received CAR T, we systematically measured high-sensitivity troponin T (hsTropT) and N-terminal pro-B natriuretic peptide (NTproBNP) at baseline and on day 1, days 7, and 21 after CAR T. Biomarker elevations with respect to timepoint and cytokine release syndrome (CRS) status were examined using repeated measure analysis of variance. hsTropT did not differ with time or with the presence of grade 2 CRS. Median hsTropT was 12.1 ng/L [interquartile range (IQR): 9.2, 20.1] at baseline, 13.1 ng/L (IQR: 9.6, 24.2) at day 1, 11.9 ng/L (IQR: 9.6, 18.0) at day 7, and 15.3 ng/L (10.8, 20.2) at day 21. In contrast, NTproBNP rose on day 1 (PWilcox = 0.0002) and day 7 (PWilcox = 2.7 × 10−5), and the degree of elevation differed by the presence of grade 2 CRS (Pinteraction = 0.002). Median NTproBNP was 179 pg/mL (IQR: 116, 325) at baseline, 357 pg/mL (IQR: 98, 813) at day 1, 420 pg/mL (IQR: 239, 1242) at day 7, and 177 pg/mL (IQR: 80, 278) at day 21. In conclusion, hsTropT l did not differ across timepoints after CAR T therapy, but NTproBNP rose at day 7, the prognostic implications of which should be the target of future research, as the indications for this therapy expand.
Highlights
Chimeric antigen receptor T-cell (CAR T) therapy against CD-19 surface antigen has shown remarkable promise in achieving durable remissions for relapsed/refractory B cell lymphomas, mantle cell lymphoma and acute lymphoblastic leukemia, with four products approved [1,2]
We examined whether cytokine release syndrome (CRS) grade and baseline abnormal/normal status impact the high-sensitivity troponin T (hsTropT) and NTproBNP change after CAR T, by including an interaction term between timepoint and CRS status in the analysis of variance (ANOVA)
We show that hsTropT remains unchanged compared to baseline, but NTproBNP rises at day 1 and peaks at day 7 post-CAR T, when the CRS incidence was shown to be the highest in previous clinical studies [4]
Summary
Chimeric antigen receptor T-cell (CAR T) therapy against CD-19 surface antigen has shown remarkable promise in achieving durable remissions for relapsed/refractory B cell lymphomas, mantle cell lymphoma and acute lymphoblastic leukemia, with four products approved (axicabtagene-ciloleucel, brexucabtagene autoleucel, tisagenlecleucel and lisocabtagene maraleucel) [1,2]. Previous analyses have raised the possibility that CAR T-cell therapies may be associated with cardiac toxicities, with an increase in troponin signifying cardiac damage, especially in the setting of CRS [6]. These were retrospective studies where troponin was checked as a result of a clinical indication and only in a subset of patients. B natriuretic peptide is a protein produced in cardiac atrial and ventricular myocytes, and their production and secretion is upregulated upon cardiac wall stress. Secretion of B natriuretic peptide and its pro-peptides is a sign of cardiac stretch, as occurs in volume overload in heart failure [8]. Whether CAR T administration systematically increases these cardiac biomarkers remains unclear
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