Clinical outcomes in posttransplant recipients of allogeneic CAR T cells
| T cell and CAR types . | Clinical reports . | No. of patients . | Incidence of GVHD . | Efficacy of CAR therapy . |
|---|---|---|---|---|
| True-allo (donor-derived DLI)* | ||||
| CD19 CAR DLI (28z; γRV) | Brudno et al | 20 | Acute: 0% Chronic: 10% (2/20) | CR 30% (n = 6) PR 10% (n = 2) |
| CD19 CAR DLI (4-1BBz; LV) | Dai et al | 2 | Acute: 100% (2/2) Chronic: 0% | CR 50% (n = 1) |
| CD19 CAR DLI (28z; SB) | Kebriaei et al | 19 | Acute: 10% (2/19) Chronic: 6% (1/19) | 63% (9 CCR, 1 CR2, 2 DIR)† |
| CD19 CAR VST (28z; γRV) | Cruz et al | 8 | 0% | CR 38% (1 CR and 2 CCR)‡ PR 13% |
| Pseudo-allo (Recipient-derived DLI)§ | ||||
| CD19 CAR “DLI” (4-1BBz; LV) | Maude et al | 18 | Acute: 0% Chronic: 0% | EFS 67%, OS 78% (at 6 months)‖ |
| CD19 CAR “DLI” (28z; γRV) | Lee et al | 8 | Acute: 0% Chronic: 0% | MRD negative CR: 37% (n=3) |
| CD19 CAR “DLI” 1:1 (4-1BBz; LV) | Turtle et al | 11 | Acute: 0% Chronic: 9% (1/11) | BM remission: 93% |
| CD19 CAR “DLI” 1:1 (4-1BBz; LV) | Gardner et al | 27 | Acute: 3% (1/27) Chronic: 0% | MRD negative remission rate: 93% |
| CD19 CAR “DLI” (28z; γRV) | Park et al | 19 | Acute: 0% Chronic: 0% | MRD negative CR: 63%¶ |
| T cell and CAR types . | Clinical reports . | No. of patients . | Incidence of GVHD . | Efficacy of CAR therapy . |
|---|---|---|---|---|
| True-allo (donor-derived DLI)* | ||||
| CD19 CAR DLI (28z; γRV) | Brudno et al | 20 | Acute: 0% Chronic: 10% (2/20) | CR 30% (n = 6) PR 10% (n = 2) |
| CD19 CAR DLI (4-1BBz; LV) | Dai et al | 2 | Acute: 100% (2/2) Chronic: 0% | CR 50% (n = 1) |
| CD19 CAR DLI (28z; SB) | Kebriaei et al | 19 | Acute: 10% (2/19) Chronic: 6% (1/19) | 63% (9 CCR, 1 CR2, 2 DIR)† |
| CD19 CAR VST (28z; γRV) | Cruz et al | 8 | 0% | CR 38% (1 CR and 2 CCR)‡ PR 13% |
| Pseudo-allo (Recipient-derived DLI)§ | ||||
| CD19 CAR “DLI” (4-1BBz; LV) | Maude et al | 18 | Acute: 0% Chronic: 0% | EFS 67%, OS 78% (at 6 months)‖ |
| CD19 CAR “DLI” (28z; γRV) | Lee et al | 8 | Acute: 0% Chronic: 0% | MRD negative CR: 37% (n=3) |
| CD19 CAR “DLI” 1:1 (4-1BBz; LV) | Turtle et al | 11 | Acute: 0% Chronic: 9% (1/11) | BM remission: 93% |
| CD19 CAR “DLI” 1:1 (4-1BBz; LV) | Gardner et al | 27 | Acute: 3% (1/27) Chronic: 0% | MRD negative remission rate: 93% |
| CD19 CAR “DLI” (28z; γRV) | Park et al | 19 | Acute: 0% Chronic: 0% | MRD negative CR: 63%¶ |
To date, 132 patients with B cell malignancies who were infused with allogeneic CD19 CAR T cells have been have reported in the published literature. Four percent (n = 5) of the patients developed acute GVHD and 3 percent (n = 4) of the patients developed chronic GVHD. More specifically, in patients who received donor-derived DLI, the total incidence of GVHD was 14% (n = 7), with an incidence of acute and chronic GVHD of 8% (n = 4) and 6% (n = 3), respectively. In patients given recipient-derived CAR T cells, the total incidence of GVHD was 2% (n = 2), with an incidence of acute and chronic GVHD of 1% (n = 1) for both.
Forty-seven patients received donor-derived CD28-based CAR T cells, of which 10% developed GVHD (n = 5; 2 acute and 3 chronic). Two patients received donor-derived 4-1BB-based CAR T cells, of which 100% (n = 2) developed GVHD (both acute). In patients given recipient-derived CD19 CAR T cells, twenty-seven patients received cells with a CD28 costimulatory molecule and none developed GVHD. Fifty-six patients received recipient-derived 4-1BB-based CAR T cells, of which 3% developed GVHD (n = 2; 1 acute and 1 chronic). These outcomes are consistent with the findings of Ghosh et al. Overall, twenty-three (40%) patients were reported to have achieved a CR, which includes those who were reported as CR or those who were reported as a continuous complete remission (CCR). The thirty-eight patients reported by Maude et al, Turtle et al, Gardner et al, and Park et al are not included in this calculation as the clinical outcomes for these patients were reported as BM remission, EFS/OS, or cumulative MRD negative remission rather than CR and PR.
BM, bone marrow; CCR, continuous complete remission; CR2, second CR; DIR, died in remission; LV, lentiviral transduction; PR, partial remission; γRL, γ-retroviral transduction; SB, Sleeping Beauty transposon.
Donor T cells were collected from the allogeneic donor (donor-derived).
The authors report that 9 patients had a CCR since transplant. Additionally, 1 patient is reported to have had a CR2, while 2 other patients died in remission (DIR).
The authors report 1 CR and 2 CCRs.
Donor T cells were collected from the recipient posttransplant (recipient-derived).
The authors report that the “EFS and OS did not differ significantly” whether or not patients had received an allo-HCT. The did not report PR or CR data for the patients.
Sixteen of the 19 patients were MRD evaluable; so the MRD negative CR rate was calculated from this subset of patients.