Clinical characteristics of patients administered escalating doses of piggyBac CAR19 T cells
| No. . | Sex, age (y) . | Disease . | Primary refractory? . | Prior auto . | Matched related allo conditioning . | DLI? . | Prior blin? . | Total prior lines of therapy . | Status at first dose CAR T . | Treated on-trial? (reason off) . | CAR19 T-cell doses administered (preceding lymphodepletion) . | Best response* (dose no. achieved) . | Duration of response, mo . | CRS† . | ICANS‡ . | Other adverse events . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F, 25 | B-ALL | No | No | MAC | No | Yes | 5 | Extra-medullary | Yes | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Cy) 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Flu/Cy) | MRD− CR (1) | 5.1 | Gr 1 | No | Cytopenias requiring support Urosepsis Death from PD |
| 2 | M, 66 | DLBCL | Yes | BEAM | RIC | 3 | No | 8 | Stage IV | Yes | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Cy) 1 × 108 TNC/m2 (Cy) | CR (2) | 18.0§ | No | No | Worsening cGVHD Pneumonia CVAD sepsis GI sepsis Death from CAR T cell malignancy‖ |
| 3 | M, 61 | B-ALL | No | No | RIC | No | No | 4 | MRD+ | Yes | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Cy) 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Flu/Cy) | MRD− CR (1) | 3.5 | No | No | Cytopenias requiring support |
| 4 | M, 42 | B-ALL | No | No | MAC | No | Yes | 5 | MRD− | No (prior seizures) | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Flu/Cy) | MRD− CR (1) | 9.2 | No | No | Cytopenias requiring support CVAD sepsis Death from PD |
| 5 | M, 18 | B-ALL | No MRD+ | No | MAC | 3 | Yes | 5 | Blasts 70% | No (IFI) | 1 × 107 TNC/m2 (Flu/Cy) 1 × 107 TNC/m2 (Flu/Cy)¶ 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Cy)# | MRD− CR (1) | 27.4§ | Gr 2 | No | Cytopenias requiring support |
| 6 | M, 18 | Burkitt | Yes | BEAM | RIC | No | No | 6 | Stage IV | No (ECOG 3) | 1 × 107 TNC/m2 (Flu/Cy) | N/A | N/A | N/A | N/A | Death from pulmonary embolus |
| 7 | M, 47 | B-ALL | No, MRD+ | No | MAC | No | Yes | 4 | BM: MRD− Occult extra-medullary | Yes | 1 × 107 TNC/m2 (Flu/Cy) | MRD− CR (1) | 9.2 | Gr 2 | No | Cytopenias requiring support |
| 8 | M, 30 | B-ALL | No | No | MAC | No | Yes | 5 | MRD+ | Yes | 1 × 107 TNC/m2 (Flu/Cy) | MRD− CR (1) | 23.2§ | No | No | CAR T malignancy Cytopenias requiring support |
| 9 | M, 20 | B-ALL | No, MRD+ | No | (1) MAC (2) MAC | 2 | No | 8 | Cerebellar mass | No (release criteria**) | 1 × 107 cells/m2 (Flu/Cy) 5 × 107 cells/m2 (Flu/Cy) 1 × 108 cells/m2 (Flu/Cy) | CR (3) | 6.0§ | Gr 2 | No | Cytopenias requiring support CVAD sepsis Death from multiviral SIRS‖ |
| 10 | F, 62 | B-ALL | No | No | RIC | No | No | 4 | Extra-medullary | Yes | 1 × 107 cells/m2 (Flu/Cy) | CR (1) | 15.6§ | No | No | Cytopenias requiring support |
| No. . | Sex, age (y) . | Disease . | Primary refractory? . | Prior auto . | Matched related allo conditioning . | DLI? . | Prior blin? . | Total prior lines of therapy . | Status at first dose CAR T . | Treated on-trial? (reason off) . | CAR19 T-cell doses administered (preceding lymphodepletion) . | Best response* (dose no. achieved) . | Duration of response, mo . | CRS† . | ICANS‡ . | Other adverse events . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F, 25 | B-ALL | No | No | MAC | No | Yes | 5 | Extra-medullary | Yes | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Cy) 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Flu/Cy) | MRD− CR (1) | 5.1 | Gr 1 | No | Cytopenias requiring support Urosepsis Death from PD |
| 2 | M, 66 | DLBCL | Yes | BEAM | RIC | 3 | No | 8 | Stage IV | Yes | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Cy) 1 × 108 TNC/m2 (Cy) | CR (2) | 18.0§ | No | No | Worsening cGVHD Pneumonia CVAD sepsis GI sepsis Death from CAR T cell malignancy‖ |
| 3 | M, 61 | B-ALL | No | No | RIC | No | No | 4 | MRD+ | Yes | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Cy) 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Flu/Cy) | MRD− CR (1) | 3.5 | No | No | Cytopenias requiring support |
| 4 | M, 42 | B-ALL | No | No | MAC | No | Yes | 5 | MRD− | No (prior seizures) | 1 × 107 TNC/m2 (Flu/Cy) 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Flu/Cy) | MRD− CR (1) | 9.2 | No | No | Cytopenias requiring support CVAD sepsis Death from PD |
| 5 | M, 18 | B-ALL | No MRD+ | No | MAC | 3 | Yes | 5 | Blasts 70% | No (IFI) | 1 × 107 TNC/m2 (Flu/Cy) 1 × 107 TNC/m2 (Flu/Cy)¶ 5 × 107 TNC/m2 (Flu/Cy) 1 × 108 TNC/m2 (Cy)# | MRD− CR (1) | 27.4§ | Gr 2 | No | Cytopenias requiring support |
| 6 | M, 18 | Burkitt | Yes | BEAM | RIC | No | No | 6 | Stage IV | No (ECOG 3) | 1 × 107 TNC/m2 (Flu/Cy) | N/A | N/A | N/A | N/A | Death from pulmonary embolus |
| 7 | M, 47 | B-ALL | No, MRD+ | No | MAC | No | Yes | 4 | BM: MRD− Occult extra-medullary | Yes | 1 × 107 TNC/m2 (Flu/Cy) | MRD− CR (1) | 9.2 | Gr 2 | No | Cytopenias requiring support |
| 8 | M, 30 | B-ALL | No | No | MAC | No | Yes | 5 | MRD+ | Yes | 1 × 107 TNC/m2 (Flu/Cy) | MRD− CR (1) | 23.2§ | No | No | CAR T malignancy Cytopenias requiring support |
| 9 | M, 20 | B-ALL | No, MRD+ | No | (1) MAC (2) MAC | 2 | No | 8 | Cerebellar mass | No (release criteria**) | 1 × 107 cells/m2 (Flu/Cy) 5 × 107 cells/m2 (Flu/Cy) 1 × 108 cells/m2 (Flu/Cy) | CR (3) | 6.0§ | Gr 2 | No | Cytopenias requiring support CVAD sepsis Death from multiviral SIRS‖ |
| 10 | F, 62 | B-ALL | No | No | RIC | No | No | 4 | Extra-medullary | Yes | 1 × 107 cells/m2 (Flu/Cy) | CR (1) | 15.6§ | No | No | Cytopenias requiring support |
allo, allogeneic HSCT; auto, autologous HSCT; BEAM, carmustine, etoposide, cytarabine, and melphalan; blin, blinatumomab; BM, bone marrow; Burkitt, Burkitt lymphoma; cGVHD, chronic graft-versus-host disease; CR, complete remission; CRS, cytokine release syndrome; CVAD, central venous access device; Cy, cyclophosphamide; DLBCL, diffuse large B cell lymphoma; DLI, donor-lymphocyte infusion; ECOG, Eastern Cooperative Oncology Group; F, female; Flu, fludarabine; GI, gastrointestinal; Gr, grade; ICANS, immune effector cell-associated neurotoxicity syndrome; IFI, invasive fungal infection; M, male; MAC, myeloablative conditioning; MRD, minimal residual disease; N/A, not applicable; PD, progressive disease; RIC, reduced intensity conditioning; SIRS, systemic inflammatory response syndrome; TNC, total nucleated cell.
B-ALL response criteria: CR, <5% bone marrow blasts, negative PET-CT scan for extramedullary disease, negative magnetic resonance imaging (MRI) for central nervous system disease; MRD− CR, absence of bone marrow MRD based on molecular testing with a limit of detection of 0.005% to 0.001%. Lymphoma response was graded according to the Lugano classification.25
CRS graded according to Lee 2014 criteria.16
ICANS graded according to the CARTOX Working Group guidelines.26
Response ongoing at last follow-up.
CAR T cell–related death.
Patient 5 developed grade 2 CRS with the initial dose of CAR19 T cells and received a repeat dose of 1 × 107 TNC/m2 before escalating to the higher dose levels.
Fludarabine was omitted at the highest cell dose for patient 5 due to persistent cytopenias.
Failure of autonomous proliferation positive control, although the product itself showed no autonomous proliferation.