Table 1.
Patient characteristics and outcomes following CAR T-cell therapy
| Characteristics | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 |
|---|---|---|---|---|---|---|---|---|---|
| Age, y | 21 | 31 | 55 | 42 | 41 | 30 | 50 | 29 | 39 |
| Sex | M | M | M | M | M | M | M | M | M |
| Disease stage | IVB | IVB | IVB | IVB | IVB | IVB | IVB | IVB | IVB |
| No. of prior therapies | 2 | 4 | 3 | 3 | 5 | 2 | 5 | 1 | 2 |
| Prior lines of therapy | 1. R-EPOCH | 1. R-EPOCH | 1. R-CHOP | 1. R-CHOP | 1. R-CHOP | 1. R-CHOP | 1. R-CHOP | 1. R-CHOP + enzastaurin | 1. R-CHOP |
| 2. R-GDP | 2. R-ICE | 2. R-ICE | 2. R-ICE | 2. R-ICE | 2. R-ICE | 2. R-ICE | 2. R-ICE | ||
| 3. R-Len | 3. R-GEMOX | 3. R-GEMOX | 3. ASCT | 3. BV + Nivo | |||||
| 4. R-GEMOX | 4. R-DHAP | 4. R-GEMOX | |||||||
| 5. R-Len | 5. R-Len | ||||||||
| Disease status | Primary-refractory | Primary-refractory | Primary-refractory | Primary-refractory | Relapsed | Primary-refractory | Primary-refractory | Relapsed | Primary-refractory |
| Baseline (Ref. range) | |||||||||
| LDH, U/L (116-245 U/L) | 872 | 509 | 343 | 577 | 342 | 293 | * | 141 | * |
| CRP, mg/dL (<0.5 mg/dL) | 2.8 | 4.3 | 7.9 | 12.4 | 0.7 | 0.5 | * | 0 | * |
| Ferritin, ng/mL (20-300 ng/mL) | 1578 | 242 | 1142 | 346 | 219 | 275 | * | 135 | * |
| MTV, mL† | 621.52 | 680.27 | 2160.83 | 1799.31 | ‡ | 711.1 | 1690 | 85.95 | ‡ |
| ECOG PS | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Bridging therapy | No | Yes | Yes | Yes | Yes | No | Yes | No | No |
| Product§ | Axi-cel | Axi-cel | Axi-cel | Axi-cel | Axi-cel | Tisa-cel | Anti-CD19 CAR (clinical trial) | Anti-CD19 CAR (clinical trial) | Axi-cel |
| CRS | Grade 1 | Grade 1 | Grade 2 | Grade 1 | Grade 2 | Grade 1 | Grade 1 | Grade 1 | Grade 1 |
| ICANS | Grade 1 | Grade 1 | Grade 2 | Grade 1 | Grade 4 | Grade 0 | Grade 2 | Grade 0 | Grade 0 |
| Tocilizumab or steroids | No | Tocilizumab | Tocilizumab and steroids | Tocilizumab | Tocilizumab and steroids | No | No | Tocilizumab | No |
| Disease response assessment|| | PET/CT, day 60; PD | PET/CT, day 60; PD | PET/CT, day 30; PD | PET/CT, day 30; PD | PET/CT, day 30; PD | PET/CT, day 90; PD | PET/CT, day 60; PD | PET/CT, day 90; PD | PET/CT, day 30; PD |
| Response to CAR T-cell therapy | Refractory | Refractory | Refractory | Refractory | Refractory | Refractory | Refractory | Refractory | Refractory |
| Biopsy confirming relapse | LN biopsy, day 74: T/HRLBCL | RP mass, day 62: T/HRLBCL | Ascites, day 40: T/HRLBCL | Pleural fluid, day 34: LBCL | Bone marrow, day 125: T/HRLBCL | Not performed | Lung lesion, day 84: T/HRLBCL | Lung lesion, day 107: T/HRLBCL | RP mass, day 50: T/HRLBCL |
| CD19 expression | |||||||||
| Pre-CAR T¶ | Yes | Yes | Yes | Yes | NA | Yes | Yes | Yes | Yes |
| Post-CAR T¶ | Yes | Yes | Yes | Yes | Yes | NA | NA | NA | NA |
| Response to subsequent anti–PD-1 therapy | Pembro, PD | Pembro, PD | Pembro, ongoing CR | Nivo, PR | Pembro, PD | ||||
| Survival status | Alive | Deceased | Deceased | Deceased | Deceased | Alive | Deceased | Alive | Deceased |
| Assays performed | mIF | mIF | FC | FC mIF, posttreatment | FC | mIF | |||
| PD-L1 | PD-L1 | PD-L1 | PD-L1 | ||||||
| FISH: disomic | FISH: disomic | FISH: amplified | FISH: disomic |
ASCT, autologous stem cell transplant; BV, brentuximab vedotin; CR, complete response; CRP, C-reactive protein; CRS, cytokine release syndrome; ECOG PS, Eastern Cooperative Oncology Group Performance Status; FC, flow cytometry; FISH, fluorescence in situ hybridization; ICANS, immune effector cell-associated neurotoxicity syndrome; LBCL, large B-cell lymphoma; LDH, lactate dehydrogenase; LN, lymph node; M, male; mIF, multispectral immunofluorescence; MTV, metabolic tumor volume; NA, not assessed; nivo, nivolumab; PD, progressive disease; Pembro, pembrolizumab; PET/CT, positron emission tomography/computed tomography; PR, partial response; R-CHOP, rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone; R-DHAP, rituximab, dexamethasone, ara-C, cisplatin; Ref., reference; R-EPOCH, rituximab, etoposide, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin; R-GDP, rituximab, gemcitabine, dexamethasone, cisplatin; R-GEMOX, rituximab, gemcitabine, oxaliplatin; R-ICE, rituximab, ifosfamide, carboplatin, etoposide; R-Len, rituximab, lenalidomide; RP, retroperitoneal.
LDH, CRP, and ferritin levels unavailable.
MTV indicates that whole-body metabolic tumor volume was ascertained from fluorodeoxyglucose (FDG)-PET/CT imaging.
PET/CT imaging unavailable for MTV calculation.
Lymphodepleting chemotherapy regimen administered: patients 1 through 5 and 7 through 9 received fludarabine (30 mg/m2 on days −5, −4, −3) and cyclophosphamide (500 mg/m2 on days −5, −4, −3); patient 6 received fludarabine (25 mg/m2 per day on days −5, −4, −3) and cyclophosphamide (250 mg/m2 per day on days −5, −4, −3).
Patients 7 and 8 achieved PR at day 30 and subsequently progressed by day 60 and day 90, respectively. All other patients experienced disease progression at their first response assessment at the indicated time points.
NA denotes patients in whom CD19 expression on tumor tissue could not be assessed due to tissue exhaustion.