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Immune reconstitution after axi-cel in lymphoma
patients at day 30 (D30) after axi-cel infusion, and included neutropenia in nine (29%) patients, anemia in five (16%) and thrombocytopenia in 13 (42%) patients.
On univariate analysis, baseline characteristics signifi- cantly associated with D30 grade 3-4 cytopenia were the Eastern Cooperative Oncology Group (ECOG) perform- ance status 1 (P=0.03), >3 prior therapies (P=0.03), and low absolute lymphocyte count (ALC) (P=0.007) (Table 1).
Hematopoietic recovery and immune reconstitution
Fifteen patients included in this analysis had ongoing remission at 1 year and 10 at 2 years (one did not have evaluable CBC). While these included both patients from ZUMA-1 and ZUMA-9, the two patients who received OOS product in cohort 2 of ZUMA-9 progressed before year 1 assessment. Among patients with ongoing remis- sion, persistent grade 3-4 cytopenias was present in four of 15 (27%) patients at 1 year and in one of nine (11%) patients at 2 years (Figure 1A to C). Among these patients, samples for flow cytometry assessment were available in nine patients at 1 year, and seven patients at 2 years. While recovery of CD8+ T cells (median 597 cells/mL; range, 143- 1,492 cells/mL) and CD56+ natural killer (NK) cells (median 118 cells/mL; range, 38-236 cells/mL) occurred in nine of nine (100%) patients by 1 year, reconstitution of CD4+ T cells
was delayed, with normalization in six of nine (67%) patients at 1 year (median 225 cells/mL; range, 108-593 cells/mL) and five of seven (71%) patients assessed at 2 years (median 263 cells/mL, range 83-1,166 cells/mL); of interest, the age of patients who did not experience CD4+ T cell normalization at 1 and 2 years ranged from 40 to 67 years. IgG levels were normal in seven of thirteen (54%) patients at 1 year (median 646 mg/dL; range, 200-1,299 mg/dL) and five of nine (56%) patients assessed at 2 years (median 552 mg/dL; range, 366-1,147 mg/dL) (Figure 1D to H). When limiting the analysis to patients who did not receive intravenous IgG (IVIG) support, four of four had normalization of IgG levels at 1 year. Interestingly, a posi- tive and significant association was observed between platelet count and CD56 cell count in ten patients with available samples for flow cytometry assessment (r=+0.64, P<0.001) (Figure 1I).
Risk of myelodysplastic syndrome
When comparing the 15 patients with grade 3-4 D30 cytopenia to the 16 patients without grade 3-4 D30 cytope- nia, the former received significantly higher number of platelet transfusions (11 of 15 [73%] vs. four of 16 [25%], P=0.01), but there was no significant difference in red blood cell transfusions (13 of 15 [87%] vs. ten of 16 [63%],
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Figure 1. Trends in hematopoietic and immune reconstitution after axi-cel therapy in patients with relapsed or refractory large B-cell lymphoma. (A to C) Hematopoietic recovery (absolute neutrophil count, hemoglobin and platelet count. (D to H) Reconstitution of absolute lymphocyte count, CD4+, CD8+, CD56+ and immunoglobulin G up to 24 months after CART infusion. (I) Correlation between CD56+ cell immune reconstitution and platelet recovery. Red dotted line indicates lower limit of normal.
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