American Society of Hematology

Figure 3.

$Clinical outcomes for patients treated with TAA-T for relapsed disease after BMT (n = 11). (A) Swimmer plot showing clinical outcomes following salvage therapy and TAA-T infusion in patients with relapsed/refractory disease after BMT, categorized by dose level (1-4). Hematologic remission was achieved in 9/11 patients prior to TAA-T infusion with postinfusion clinical outcomes defined as CCR, PR, stable disease (SD), PD, and relapse. Patients in hematologic remission with MRD are noted as CCR*. Patients who did not achieve hematologic remission are noted as + (P3, P11). The dotted line denotes 1 year postinfusion. (B) Kaplan-Meier curve estimating LFS postinfusion of relapsed patients. One-year LFS 27.3%; median LFS was 64 days. Patients characterized as responders (CCR within 3 months of first TAA-T infusion; n = 4) had prolonged median LFS (839 days) compared with nonresponders (PD/R within 3 months of first TAA-T infusion; n = 7); median LFS was 42 days (P = .003). (C) Kaplan-Meier curve estimating OS postinfusion of relapsed patients. One-year OS was 36.36% with median survival of 255 days post–TAA-T infusion. Responders had prolonged median OS (1150 days) compared with nonresponders (150 days) (P = .003). (D) One-year postrelapse OS was 42% in early relapsers (patients with relapse within 6 months of transplant; n = 7) who received TAA-T infusion. (E) Qualitative grading of immunofluorescence expression of TAA targets (WT1, PRAME, and survivin) on blast population and clinical outcomes following TAA-T of evaluable patients with relapsed AML posttransplant. The paraffin-embedded tissues were deparaffinized and incubated post–antigen retrieval with anti-survivin, anti–Wilms tumor protein (abcam), and anti-PRAME (Sigma) followed by Alexa Fluor568 (Texas red channel) donkey anti-rabbit IgG secondary antibody for survivin and PRAME (abcam) and AlexaFluor488 (FITC) donkey anti-mouse IgG secondary antibody for WT1 (abcam). The sections were mounted with DAPI staining solution (abcam), and the images were captured at 20× magnification on an Olympus BX53-DP73 microscope using cellSens software. Clinical outcomes characterized as responder and nonresponder (as above). (F) Disease course and TCR unique clonotype frequencies over time for P5 with MDS/AML, relapsed 117 days posttransplant and subsequently achieved CR with salvage therapy (azacitidine) prior to TAA-T infusion. Hematologic relapse with peripheral blasts cleared with a second TAA-T infusion, azacitidine, and lenalidomide, though remained MRD+. (G) Disease course and unique TCR clonotype frequency over time for P8, a pediatric patient with Ph+ B-cell ALL with persistent BCR/ABL positivity posttransplant despite treatment with dasatinib. Briefly achieved BCR/ABL negativity following first TAA-T infusion followed by rise in BCR/ABL quantification ratio following the second TAA-T infusion. DAPI, 4′,6-diamidino-2-phenylindole; IgG, immunoglobulin G.$

Clinical outcomes for patients treated with TAA-T for relapsed disease after BMT (n = 11). (A) Swimmer plot showing clinical outcomes following salvage therapy and TAA-T infusion in patients with relapsed/refractory disease after BMT, categorized by dose level (1-4). Hematologic remission was achieved in 9/11 patients prior to TAA-T infusion with postinfusion clinical outcomes defined as CCR, PR, stable disease (SD), PD, and relapse. Patients in hematologic remission with MRD are noted as CCR*. Patients who did not achieve hematologic remission are noted as + (P3, P11). The dotted line denotes 1 year postinfusion. (B) Kaplan-Meier curve estimating LFS postinfusion of relapsed patients. One-year LFS 27.3%; median LFS was 64 days. Patients characterized as responders (CCR within 3 months of first TAA-T infusion; n = 4) had prolonged median LFS (839 days) compared with nonresponders (PD/R within 3 months of first TAA-T infusion; n = 7); median LFS was 42 days (P = .003). (C) Kaplan-Meier curve estimating OS postinfusion of relapsed patients. One-year OS was 36.36% with median survival of 255 days post–TAA-T infusion. Responders had prolonged median OS (1150 days) compared with nonresponders (150 days) (P = .003). (D) One-year postrelapse OS was 42% in early relapsers (patients with relapse within 6 months of transplant; n = 7) who received TAA-T infusion. (E) Qualitative grading of immunofluorescence expression of TAA targets (WT1, PRAME, and survivin) on blast population and clinical outcomes following TAA-T of evaluable patients with relapsed AML posttransplant. The paraffin-embedded tissues were deparaffinized and incubated post–antigen retrieval with anti-survivin, anti–Wilms tumor protein (abcam), and anti-PRAME (Sigma) followed by Alexa Fluor568 (Texas red channel) donkey anti-rabbit IgG secondary antibody for survivin and PRAME (abcam) and AlexaFluor488 (FITC) donkey anti-mouse IgG secondary antibody for WT1 (abcam). The sections were mounted with DAPI staining solution (abcam), and the images were captured at 20× magnification on an Olympus BX53-DP73 microscope using cellSens software. Clinical outcomes characterized as responder and nonresponder (as above). (F) Disease course and TCR unique clonotype frequencies over time for P5 with MDS/AML, relapsed 117 days posttransplant and subsequently achieved CR with salvage therapy (azacitidine) prior to TAA-T infusion. Hematologic relapse with peripheral blasts cleared with a second TAA-T infusion, azacitidine, and lenalidomide, though remained MRD⁺. (G) Disease course and unique TCR clonotype frequency over time for P8, a pediatric patient with Ph⁺ B-cell ALL with persistent BCR/ABL positivity posttransplant despite treatment with dasatinib. Briefly achieved BCR/ABL negativity following first TAA-T infusion followed by rise in BCR/ABL quantification ratio following the second TAA-T infusion. DAPI, 4′,6-diamidino-2-phenylindole; IgG, immunoglobulin G.

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