Figure 4.
Relapse after treatment with CD19 CAR T cells. (A) Cumulative incidence of CD19+ (red line) and CD19– (blue line) relapse after CD19 CAR T-cell therapy. (B-C) Patients who subsequently developed CD19+ relapse had a lower peak (4.34 vs 5.18 log10 transgene copies per μg of DNA; P = .034) and AUC from day 28 to day 90 (AUC28-90; 5.47 vs 6.60 log10 transgene copies per μg of DNA; P = .0042) of CAR T cells in the blood compared with those who developed CD19– relapse. (B) Each thin line represents a single patient; the bold lines represent the averaged data using LOESS curve fitting approximation with the standard error shown in pink and light blue. (D) Swimmer plots demonstrating CAR T-cell counts in the blood from day 0 to day 600 in patients who either did not relapse (left) or who relapsed with CD19+ (center) or CD19– (right) disease. The timing of B-cell recovery (Ο), relapse (+), allogeneic HCT (⋄), and death (Δ) are shown. Patients 17, 27, 29, and 34 died on days 608, 818, 1079, and 1174, respectively. All patients who developed CD19– relapse (right panel) had detectable levels of CAR T cells in the blood at the last time point before relapse and ongoing B-cell aplasia. CAR T-cell counts in the blood were measured by qPCR to detect FlapEF1α and are reported as transgene copies per μg of DNA in the color-coded legend. Patients 24, 25, 26, 28, 30, 32, 33, 34, 35, and 36 received a second infusion of CAR T cells after relapse.

Relapse after treatment with CD19 CAR T cells. (A) Cumulative incidence of CD19+ (red line) and CD19 (blue line) relapse after CD19 CAR T-cell therapy. (B-C) Patients who subsequently developed CD19+ relapse had a lower peak (4.34 vs 5.18 log10 transgene copies per μg of DNA; P = .034) and AUC from day 28 to day 90 (AUC28-90; 5.47 vs 6.60 log10 transgene copies per μg of DNA; P = .0042) of CAR T cells in the blood compared with those who developed CD19 relapse. (B) Each thin line represents a single patient; the bold lines represent the averaged data using LOESS curve fitting approximation with the standard error shown in pink and light blue. (D) Swimmer plots demonstrating CAR T-cell counts in the blood from day 0 to day 600 in patients who either did not relapse (left) or who relapsed with CD19+ (center) or CD19 (right) disease. The timing of B-cell recovery (Ο), relapse (+), allogeneic HCT (⋄), and death (Δ) are shown. Patients 17, 27, 29, and 34 died on days 608, 818, 1079, and 1174, respectively. All patients who developed CD19 relapse (right panel) had detectable levels of CAR T cells in the blood at the last time point before relapse and ongoing B-cell aplasia. CAR T-cell counts in the blood were measured by qPCR to detect FlapEF1α and are reported as transgene copies per μg of DNA in the color-coded legend. Patients 24, 25, 26, 28, 30, 32, 33, 34, 35, and 36 received a second infusion of CAR T cells after relapse.

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