Figure 3.
Unique CAR T cell–associated toxicities and CAR T-cell expansion in select patients (n = 2) with non-CNS EMD. (A) CT scans obtained pre– and post–CD22 CAR infusion showing CAR T cell–associated pulmonary toxicity in a subject (Patient 6) with pleural-based non-CNS EMD. Clinically, CAR T-cell trafficking to non-CNS EMD was evidenced by development of new pleural effusions, ground-glass opacities, and oxygen requirement. (B) Corresponding flow cytometry of pleural fluid before CD22 CAR infusion identified B-ALL comprising 88% of mononuclear cells (MNCs). B-ALL blasts (navy blue) expressed slightly dim CD45, CD19, CD10, partial CD34, CD22, dim CD38, and CD24. CD22 antibody-binding capacity (ABC) was 912, a quantitative measure of antigen site density on the blast cell surface. Subsequently, flow cytometry performed at day +16 post–CD22 CAR infusion showed an expansion of CD22 CAR T cells (green), comprising 72% of T cells, which persisted at day +27. The amount of B-ALL disease decreased to 58% of MNCs and 19% of MNCs at day +16 and day +27, respectively. CD22 ABC decreased posttherapy from 912 to 611 and 269 at day +16 and day +27, respectively. Flow cytometry was also performed on bronchoalveolar lavage post–CAR infusion. The amount of B-ALL disease decreased from 52% of MNCs at day +7 to 30% of MNCs at day +31. At day +7, 1.8% of T cells were CD22 CAR T cells (green); they expanded to comprise 74% of T cells at day +31. (C) CT scans obtained pre– and post–CD22 CAR infusion in a subject (Patient 39) with pleural-based disease exhibiting delayed resolution (day +83) of CAR T cell–associated inflammatory toxicities. (D) Corresponding flow cytometry of pleural fluid before CD22 CAR T-cell therapy identified B-ALL comprising 86% of MNCs. B-ALL blasts (navy blue) expressed a spectrum of CD45 from dim to negative, bright CD10, CD34, CD22, and dim CD38; they were negative for CD19 and CD24. The CD22 ABC was 2594. As expected, no CAR T cells were detected by using the flow cytometry assay. Subsequently, flow cytometry was performed on a bronchoalveolar lavage specimen at day +54 post–CD22 CAR infusion. Expansion of CD22 CAR T cells was detected (green), comprising 85% of T cells, and there was no evidence of B-ALL. Notably, Patient 39 did not have non-CNS EMD identifiable on FDG PET/CT imaging during central review and was not included in the initial study cohort. (E) Generalized approach to indications for evaluation of non-CNS EMD in the peri–CAR T-cell setting. SSA, side scatter area.

Unique CAR T cell–associated toxicities and CAR T-cell expansion in select patients (n = 2) with non-CNS EMD. (A) CT scans obtained pre– and post–CD22 CAR infusion showing CAR T cell–associated pulmonary toxicity in a subject (Patient 6) with pleural-based non-CNS EMD. Clinically, CAR T-cell trafficking to non-CNS EMD was evidenced by development of new pleural effusions, ground-glass opacities, and oxygen requirement. (B) Corresponding flow cytometry of pleural fluid before CD22 CAR infusion identified B-ALL comprising 88% of mononuclear cells (MNCs). B-ALL blasts (navy blue) expressed slightly dim CD45, CD19, CD10, partial CD34, CD22, dim CD38, and CD24. CD22 antibody-binding capacity (ABC) was 912, a quantitative measure of antigen site density on the blast cell surface. Subsequently, flow cytometry performed at day +16 post–CD22 CAR infusion showed an expansion of CD22 CAR T cells (green), comprising 72% of T cells, which persisted at day +27. The amount of B-ALL disease decreased to 58% of MNCs and 19% of MNCs at day +16 and day +27, respectively. CD22 ABC decreased posttherapy from 912 to 611 and 269 at day +16 and day +27, respectively. Flow cytometry was also performed on bronchoalveolar lavage post–CAR infusion. The amount of B-ALL disease decreased from 52% of MNCs at day +7 to 30% of MNCs at day +31. At day +7, 1.8% of T cells were CD22 CAR T cells (green); they expanded to comprise 74% of T cells at day +31. (C) CT scans obtained pre– and post–CD22 CAR infusion in a subject (Patient 39) with pleural-based disease exhibiting delayed resolution (day +83) of CAR T cell–associated inflammatory toxicities. (D) Corresponding flow cytometry of pleural fluid before CD22 CAR T-cell therapy identified B-ALL comprising 86% of MNCs. B-ALL blasts (navy blue) expressed a spectrum of CD45 from dim to negative, bright CD10, CD34, CD22, and dim CD38; they were negative for CD19 and CD24. The CD22 ABC was 2594. As expected, no CAR T cells were detected by using the flow cytometry assay. Subsequently, flow cytometry was performed on a bronchoalveolar lavage specimen at day +54 post–CD22 CAR infusion. Expansion of CD22 CAR T cells was detected (green), comprising 85% of T cells, and there was no evidence of B-ALL. Notably, Patient 39 did not have non-CNS EMD identifiable on FDG PET/CT imaging during central review and was not included in the initial study cohort. (E) Generalized approach to indications for evaluation of non-CNS EMD in the peri–CAR T-cell setting. SSA, side scatter area.

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