Outcome of patients who received a repeat CD19-CAR T cell infusion using a previously manufactured cellular product
| Patient no. . | Prior CAR+ T cell per kg dose . | Days from first infusion to first relapse . | CD19- expression . | Sites of recurrent detectable disease . | Subsequent therapies/response . | CAR T-cell reinfusion treatment characteristics . |
|---|---|---|---|---|---|---|
| 4 | 1 × 106 | 70 | Positive | EM | Focal RT to EM site and CD3-depleted DLI → improved PET → BM relapse∗ → CAR infusion #2 → NR (NGS = 16 clones per million) → progressive disease (combined BM∗/EM; 57 d after infusion) → palliative therapy → died secondary to disease | Preinfusion marrow MRD 0.052%; intensified† LD; dose: 3 × 106 CAR+ T cells per kg |
| 5 | 1 × 106 | 271 | Positive | BM | Methotrexate/mercaptopurine → CAR infusion #2 → MRDneg CR (NGS = 0 clones per million) → HCT #2 → died secondary to transplant related toxicity | Preinfusion marrow MRD 0.165%; intensified† LD; dose: 3 × 106 CAR+ T cells per kg; grade 2 CRS (tocilizumab ×2) |
| 6 | 1 × 106 | 160 | Positive | BM∗/EM | Chloroma excision → CAR infusion #2 with pembrolizumab → MRDneg CR (NGS = 0 clones per million) and improved PET → consolidative RT to prior EM site → relapse (combined BM [NGS = 189 clones per million]/EM; 183 d after infusion) → CAR infusion #3 → MRDneg CR (NGS = 0 clones per million) and improved PET → consolidative RT to prior EM site → loss of BCA → CAR infusion #4 → BCA with continued disease remission | CAR Infusion #2: before infusion marrow MRD 0.006%; nonintensified LD; dose: 1 × 106 CAR+ T cells per kg; immune mediated side effects (felt to be pembrolizumab-related) CAR Infusion #3: before infusion marrow MRD 7.605%; intensified LD; dose: 3 × 106 CAR+ T cells per kg; grade 1 CRS (tocilizumab ×1) CAR Infusion #4: before infusion marrow MRD negative (NGS 0); intensified LD; dose: 3 × 106 CAR+ T cells per kg; grade 1 CRS |
| Patient no. . | Prior CAR+ T cell per kg dose . | Days from first infusion to first relapse . | CD19- expression . | Sites of recurrent detectable disease . | Subsequent therapies/response . | CAR T-cell reinfusion treatment characteristics . |
|---|---|---|---|---|---|---|
| 4 | 1 × 106 | 70 | Positive | EM | Focal RT to EM site and CD3-depleted DLI → improved PET → BM relapse∗ → CAR infusion #2 → NR (NGS = 16 clones per million) → progressive disease (combined BM∗/EM; 57 d after infusion) → palliative therapy → died secondary to disease | Preinfusion marrow MRD 0.052%; intensified† LD; dose: 3 × 106 CAR+ T cells per kg |
| 5 | 1 × 106 | 271 | Positive | BM | Methotrexate/mercaptopurine → CAR infusion #2 → MRDneg CR (NGS = 0 clones per million) → HCT #2 → died secondary to transplant related toxicity | Preinfusion marrow MRD 0.165%; intensified† LD; dose: 3 × 106 CAR+ T cells per kg; grade 2 CRS (tocilizumab ×2) |
| 6 | 1 × 106 | 160 | Positive | BM∗/EM | Chloroma excision → CAR infusion #2 with pembrolizumab → MRDneg CR (NGS = 0 clones per million) and improved PET → consolidative RT to prior EM site → relapse (combined BM [NGS = 189 clones per million]/EM; 183 d after infusion) → CAR infusion #3 → MRDneg CR (NGS = 0 clones per million) and improved PET → consolidative RT to prior EM site → loss of BCA → CAR infusion #4 → BCA with continued disease remission | CAR Infusion #2: before infusion marrow MRD 0.006%; nonintensified LD; dose: 1 × 106 CAR+ T cells per kg; immune mediated side effects (felt to be pembrolizumab-related) CAR Infusion #3: before infusion marrow MRD 7.605%; intensified LD; dose: 3 × 106 CAR+ T cells per kg; grade 1 CRS (tocilizumab ×1) CAR Infusion #4: before infusion marrow MRD negative (NGS 0); intensified LD; dose: 3 × 106 CAR+ T cells per kg; grade 1 CRS |
DLI, donor lymphocyte infusion; EM, extramedullary disease (PET- and biopsy-proven CD19-positive disease); HCT, hematopoietic cell transplant; LD, lymphodepletion; RT, radiation therapy.
MRD testing positive by flow cytometry.
Intensified LD regimen administrated of fludarabine 40mg/m2 on days −4, −3, and −2, and cyclophosphamide 600 mg/m2 on days −3 and −2.