Hypomagnesemia in lymphoma patients receiving CAR T therapy correlates with immune dysfunction and decreased survival.
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Gile Jennifer J, Mondello Patrizia, Wang Zixing, Li Ying, Bansal Radhika, Gandhi Sangeetha, Zhang Henan, Babadi Elham, Martinez Kodi, McCoy Gabrielle, Shao Zuoyi, Regan Kevin, Hathcock Matthew A, Wang Panwen, Wang Junwen, Al Saleh Abdullah S, Ruan Gordon, Ansell Stephen M, Bennani N Nora, Johnston Patrick B, Paludo Jonas, Villasboas-Bisneto Jose C, Khurana Arushi, Durani Urshila, Wang Yucai, Hampel Paul J, Rosenthal Allison, Munoz Javier, Moreno Eider, Castro Januario E, Murthy Hemant S, Kharfan-Dabaja Mohamed, Kenderian Saad S, Kim Jenny J, Shen Rhine, Mattie Mike, Lin Yi, Witzig Thomas E
Аннотация
METHODS: Patients with LBCL who received axi-cel under the ZUMA-1 trial or as FDA approved therapy at Mayo Clinic were examined. Serum samples were obtained at specified time points and cytokine analysis was performed. Single cell RNA sequencing was performed on peripheral blood mononuclear cells. The Student T-test, Kruskal Wallis, or Fisher's Exact Tests were used to compare differences in demographics across Mg levels. Survival curves were plotted using the Kaplan-Meier methodology and compared using the Wilcoxon test.
RESULTS: We found that hypomagnesemia before lymphodepletion chemotherapy predicted inferior progression-free and overall survival in the pivotal study ZUMA-1 (NCT02348216). These results were validated in an independent cohort of LBCL patients receiving axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Hypomagnesemia correlated with increased inflammatory serum markers and cytokine levels including ferritin, IL-6, IL1Ra, IL-8, and MIP1a. scRNAseq analysis unveiled altered immune interactions between monocytes and T cells with a concordant immune suppressive transcriptome.
CONCLUSIONS: Hypomagnesemia at the time of CAR-T infusion is associated with an unfavorable inflammatory profile and decreased response and survival in LBCL patients receiving axi-cel. These findings suggest a potentially actionable prognostic factor for patients with large cell lymphoma undergoing CAR-T.