Risk factors of tumor lysis syndrome in relapsed/refractory multiple myeloma patients undergoing BCMA CAR-T cell therapy.

OBJECTIVE: To investigate the risk factors of tumor lysis syndrome (TLS) in relapsed/refractory multiple myeloma (MM) patients undergoing B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy. METHOD: The clinical data of 99 relapsed/refractory MM patients receiving BCMA CAR-T cell therapy in the First Affiliated Hospital, Zhejiang University School of Medicine from July 2018 to December 2021 were collected in this study. Univariate analysis and multivariate logistic regression were performed to evaluate the risk factors of TLS following BCMA CAR-T cell therapy. RESULTS: Among the 99 patients, TLS occurred in 17 cases (17.2%) with an onset time of (8.9±3.0) d after BCMA CAR-T cell therapy. All TLS patients developed TLS-related clinical manifestations, including 17 cases with renal dysfunction, 8 cases with arrhythmia. All TLS patients developed cytokine release syndrome (CRS) with an onset of 1.0 (1.0, 6.5) d after CAR-T cell therapy, and 13 cases developed grade 3-4 CRS. The levels of serum uric acid, serum creatinine and the ratio of cases with grade 3-4 CRS were significantly higher in TLS patients than in non-TLS patients (all P<0.05). Multivariate logistic regression revealed that serum creatinine ( OR=1.015, P<0.01) and severe CRS ( OR=9.371, P<0.01) were independent risk factors of TLS. CONCLUSIONS: Relapsed/refractory MM patients undergoing BCMA CAR-T therapy shows high incidence of TLS, which are related to elevated levels of serum creatinine and severe CRS. TLS can be prevented clinically by reducing serum creatinine and controlling CRS severity.

Risk factors of acute kidney injury during BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma.

OBJECTIVE: To explore the risk factors of acute kidney injury (AKI) during B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy in patients with relapsed/refractory multiple myeloma (MM). METHODS: The clinical data of 99 patients with relapsed/refractory MM who received BCMA CAR-T cell therapy in the First Affiliated Hospital of Zhejiang University School of Medicine from July 2018 to December 2021 was retrospectively analyzed. Dynamic changes of renal function before and after chemotherapy preconditioning and after CAR-T cell infusion were observed. Logistic regression was used to analyze the independent risk factors associated with the occurrence of AKI. RESULTS: Among 99 patients, the AKI occurred in 25 cases with an incidence rate of 25.3%, and the median time was 8.0 (5.5,11.0) d. The AKI grade 1, 2 and 3 accounted for 8.0%, 12.0% and 36.0%, respectively. Logistic regression analysis showed that serum creatinine (SCr) after chemotherapy preconditioning ( OR=1.020, P<0.001), and the grade of cytokine release syndrome (CRS) ( OR=6.501, P<0.01) were independent risk factors for AKI during treatment. The area under the ROC curve (AUC) of SCr after chemotherapy preconditioning in predicting AKI was 0.800 (95% CI: 0.694-0.904, P<0.001); using 83.0 µmol/L as cut-off value, the sensitivity, specificity and Youden index of SCr were 72.0%, 80.8% and 0.528, respectively. The incidence of AKI in patients with grade 3-4 CRS was 39.1%, while that was 13.2% in patients with CRS

Activating the Bifunctionality of a Perovskite Oxide toward Oxygen Reduction and Oxygen Evolution Reactions.

This article presents a facile and effective approach to activate the bifunctionality of calcium-manganese perovskites toward the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). We substituted Nb into the Mn site of CaMnO3 (CMO) and treated the material with H2. The as-obtained CaMn0.75Nb0.25O3-δ (H2-CMNO) displays the same structure as that of CMO, and compared to that of CMO, H2-CMNO exhibits significantly improved OER performance, including a lower overpotential, a reduced Tafel slope, a higher mass activity, and enhanced stability. In addition, the ORR performance of H2-CMNO is also greatly enhanced, relative to CMO, with a higher ORR activity and a more efficient electron-transfer pathway. H2-CMNO shows an even higher activity-per-catalyst cost and superior stability than that of state-of-the-art materials, such as IrO2 and Pt/C. This great enhancement in ORR and OER activity of H2-CMNO is attributed to several factors, including phase stabilization, optimized eg filling, better OH- adsorption, and improved electrical conductivity.