Clinical lymphoma, myeloma & leukemia · 2023
Significance of alkaline Phosphatase After Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma.
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Dong Rujiao, Wang Yudi, Sun Xiaohong, Lin Yuanyuan, Luo Yuqing, Xing Chongyun, Sun Lan, Zhang Shenghui, Yu Kang, Jiang Songfu, Chen Yi
Аннотация
BACKGROUND: The inexpensive and readily available biomarkers for cytokine release syndrome (CRS) grading and prognosis assessment in chimeric antigen receptor (CAR)-T therapy are currently lacking. This study examined the significance of alkaline phosphatase (ALP) after CAR-T therapy in patients with relapsed/refractory multiple myeloma (MM).
METHODS: This cohort study included 27 patients with relapsed/refractory MM who were treated with CAR-T cells between December 2017 and October 2021. Patients were classified into 2 groups: normal ALP group (peak ALP <125 U/L, n = 10) and high ALP group (peak ALP ≥125 U/L, n = 17).
RESULTS: Within 1 month of CAR-T cell infusion, the incidence of ALP increases was 63%. We found that ALP levels began to rise in the second week, peaked in the third and fourth weeks, and began to decline in the second month. Moreover, the ALP levels in previous chemotherapy-responsive period were significantly lower than those after CAR-T therapy. Statistical analysis found that patients with increased ALP exhibited higher alanine aminotransferase and aspartate aminotransferase levels, higher and longer CAR-T cell proliferation, more serious CRS, higher cytokine and ferritin levels, and higher initial response rates. In addition, the duration of ALP increase was parallel to the duration of CAR-T expansion. Multivariable Cox-regression analysis showed that peak ALP was the independent predictor for progression-free survival (PFS) (HR = 0.029, 95% CI: 0.002-0.369).
CONCLUSIONS: Our results suggest that the ALP levels after CAR-T therapy could serve as a suitable biomarker for monitoring CAR-T cell proliferation, CRS grading, and prognosis in patients with MM.
METHODS: This cohort study included 27 patients with relapsed/refractory MM who were treated with CAR-T cells between December 2017 and October 2021. Patients were classified into 2 groups: normal ALP group (peak ALP <125 U/L, n = 10) and high ALP group (peak ALP ≥125 U/L, n = 17).
RESULTS: Within 1 month of CAR-T cell infusion, the incidence of ALP increases was 63%. We found that ALP levels began to rise in the second week, peaked in the third and fourth weeks, and began to decline in the second month. Moreover, the ALP levels in previous chemotherapy-responsive period were significantly lower than those after CAR-T therapy. Statistical analysis found that patients with increased ALP exhibited higher alanine aminotransferase and aspartate aminotransferase levels, higher and longer CAR-T cell proliferation, more serious CRS, higher cytokine and ferritin levels, and higher initial response rates. In addition, the duration of ALP increase was parallel to the duration of CAR-T expansion. Multivariable Cox-regression analysis showed that peak ALP was the independent predictor for progression-free survival (PFS) (HR = 0.029, 95% CI: 0.002-0.369).
CONCLUSIONS: Our results suggest that the ALP levels after CAR-T therapy could serve as a suitable biomarker for monitoring CAR-T cell proliferation, CRS grading, and prognosis in patients with MM.