Severe hypophosphatemia following idecabtagene vicleucel regardless of the severity of cytokine release syndrome.

Background Aims: Hypophosphatemia has been recently recognized adverse event in chimeric antigen receptor (CAR)-T cell therapy, complicating 70-75% of patients. Severe hypophosphatemia can cause cytokine release syndrome (CRS)-like symptoms, such as respiratory and cardiovascular dysfunction. Some reports have described the association between inorganic phosphate (iP) and CRS in patients treated with tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), axicabtagene ciloleucel (axi-cel). However, the association between iP and idecabtagene vicleucel (ide-cel) has not been reported and the kinetics of serum iP for each CAR-T cell product have not been compared. We aimed to analyze the kinetics of iP with CAR-T cell products, including ide-cel, and the association between hypophosphatemia and severe CRS.

Methods: We retrospectively analyzed patients aged ≥ 18 years with B-cell malignancies who received CAR-T cell therapy in our institution. All available laboratory data were collected for 21 days after CAR-T cell infusion; clinical and laboratory data were extracted from electronic medical records.

Results: A total of 108 patients were treated with CAR-T cell therapy (tisa-cel, n = 56; liso-cel, n = 11; axi-cel, n = 28; ide-cel, n = 13). The cumulative incidence of hypophosphatemia and severe hypophosphatemia were significantly higher in the ide-cel group than the other CAR-T products group (92.3% versus 67.5%, P = 0.0045, and 15.4% versus 2.1%, P = 0.017), Patients treated with ide-cel had significantly lower serum iP levels from day -4 to 8 compared to other CAR-T products. As previous reports, the cumulative incidence of hypophosphatemia in the other CAR-T products group was significantly higher in the severe CRS group than in the mild CRS group (84.0% versus 60.0%, P = 0.0002). In contrast, there was no significant difference between the two groups in the ide-cel group (65% versus 100%, P = 0.13).

Conclusion: Our results suggest that and that it is important to monitor iP kinetics more carefully because patients treated with ide-cel complicate severe hypophosphatemia, regardless of CRS severity.