Outcomes of patients with R/R CNS disease categorized into separate cohorts
| Outcome . | CNS disease (n = 40)* . | |||||
|---|---|---|---|---|---|---|
| iCNS (n = 23) . | CNS + BM (n = 17) . | P . | CNS+ (n = 9) . | CNS– (n = 31) . | P . | |
| CRS | .71 | .55 | ||||
| Grade 1 | 9 | 6 | 2 | 13 | ||
| Grade 2 | 3 | 2 | 1 | 4 | ||
| Grade 3 | 2 | 1 | 0 | 3 | ||
| Grade 4 | 0 | 2 | 0 | 2 | ||
| Unknown | 1 | 0 | 1 | 0 | ||
| ICANS | .22 | 1.0 | ||||
| Grade 1 | 5 | 4 | 3 | 6 | ||
| Grade 2 | 2 | 0 | 1 | 1 | ||
| Grade 3 | 0 | 1 | 0 | 1 | ||
| Grade 4 | 0 | 2 | 0 | 2 | ||
| Response | .07 | .54 | ||||
| No CR | 1 | 3 | 2 | 2 | ||
| CR (% MRD negative) | 22 (100%) | 13 (92%) | 7 (100%) | 28 (96%) | ||
| Died before day 28 | 0 | 1 | 0 | 1 | ||
| Relapsed post-CAR | 7 | 8 | .34 | 5 | 10 | .26 |
| Site of relapse | .18 | .32 | ||||
| CNS | 4 | 1 | 3 | 2 | ||
| CNS + BM | 0 | 2 | 0 | 2 | ||
| BM only | 3 | 5 | 2 | 6 | ||
| BM + other EM | 0 | 0 | 0 | 0 | ||
| Other EM disease | 0 | 0 | 0 | 0 | ||
| CD19-negative relapse | 2/7 | 3/8 | 1.0 | 1/5 | 4/10 | 1.0 |
| Unknown | 1 | 1 | 1 | 1 | ||
| Time from infusion to relapse, d | 178 (30-577) | 61 (27-266) | .20 | 174 (30-577) | 81.5 (27-206) | .54 |
| SCT post-CAR | 2 | 4 | 0.37 | 2 | 4 | .60 |
| Rationale for SCT post-CAR | 0.23 | .54 | ||||
| Preemptive | 0 | 1 | 0 | 1 | ||
| Loss of BCA | 0 | 0 | 0 | 0 | ||
| Refractory/relapse | 1 | 3 | 2 | 2 | ||
| MLL rearranged | 1 | 0 | 0 | 1 | ||
| Alive/dead | 20/3 | 11/6 | 0.13 | 7/2 | 24/7 | 1.0 |
| Cause of death | 1.0 | 1.0 | ||||
| Relapse | 2 | 5 | 2 | 5 | ||
| Infection | 1 | 1 | 0 | 2 | ||
| CRS | 0 | 0 | 0 | 0 | ||
| Neurotoxicity | 0 | 0 | 0 | 0 | ||
| Transplant related | 0 | 0 | 0 | 0 | ||
| Cardiac related | 0 | 0 | 0 | 0 | ||
| Loss of BCA | 5 | 5 | 0.72 | 3 | 7 | .67 |
| Time from infusion to loss of BCA, d | 146 (36-192) | 174 (148-266) | .48 | 114 (36-192) | 174 (101-266) | .56 |
| Outcome . | CNS disease (n = 40)* . | |||||
|---|---|---|---|---|---|---|
| iCNS (n = 23) . | CNS + BM (n = 17) . | P . | CNS+ (n = 9) . | CNS– (n = 31) . | P . | |
| CRS | .71 | .55 | ||||
| Grade 1 | 9 | 6 | 2 | 13 | ||
| Grade 2 | 3 | 2 | 1 | 4 | ||
| Grade 3 | 2 | 1 | 0 | 3 | ||
| Grade 4 | 0 | 2 | 0 | 2 | ||
| Unknown | 1 | 0 | 1 | 0 | ||
| ICANS | .22 | 1.0 | ||||
| Grade 1 | 5 | 4 | 3 | 6 | ||
| Grade 2 | 2 | 0 | 1 | 1 | ||
| Grade 3 | 0 | 1 | 0 | 1 | ||
| Grade 4 | 0 | 2 | 0 | 2 | ||
| Response | .07 | .54 | ||||
| No CR | 1 | 3 | 2 | 2 | ||
| CR (% MRD negative) | 22 (100%) | 13 (92%) | 7 (100%) | 28 (96%) | ||
| Died before day 28 | 0 | 1 | 0 | 1 | ||
| Relapsed post-CAR | 7 | 8 | .34 | 5 | 10 | .26 |
| Site of relapse | .18 | .32 | ||||
| CNS | 4 | 1 | 3 | 2 | ||
| CNS + BM | 0 | 2 | 0 | 2 | ||
| BM only | 3 | 5 | 2 | 6 | ||
| BM + other EM | 0 | 0 | 0 | 0 | ||
| Other EM disease | 0 | 0 | 0 | 0 | ||
| CD19-negative relapse | 2/7 | 3/8 | 1.0 | 1/5 | 4/10 | 1.0 |
| Unknown | 1 | 1 | 1 | 1 | ||
| Time from infusion to relapse, d | 178 (30-577) | 61 (27-266) | .20 | 174 (30-577) | 81.5 (27-206) | .54 |
| SCT post-CAR | 2 | 4 | 0.37 | 2 | 4 | .60 |
| Rationale for SCT post-CAR | 0.23 | .54 | ||||
| Preemptive | 0 | 1 | 0 | 1 | ||
| Loss of BCA | 0 | 0 | 0 | 0 | ||
| Refractory/relapse | 1 | 3 | 2 | 2 | ||
| MLL rearranged | 1 | 0 | 0 | 1 | ||
| Alive/dead | 20/3 | 11/6 | 0.13 | 7/2 | 24/7 | 1.0 |
| Cause of death | 1.0 | 1.0 | ||||
| Relapse | 2 | 5 | 2 | 5 | ||
| Infection | 1 | 1 | 0 | 2 | ||
| CRS | 0 | 0 | 0 | 0 | ||
| Neurotoxicity | 0 | 0 | 0 | 0 | ||
| Transplant related | 0 | 0 | 0 | 0 | ||
| Cardiac related | 0 | 0 | 0 | 0 | ||
| Loss of BCA | 5 | 5 | 0.72 | 3 | 7 | .67 |
| Time from infusion to loss of BCA, d | 146 (36-192) | 174 (148-266) | .48 | 114 (36-192) | 174 (101-266) | .56 |
ICANS, immune effector cell-associated neurotoxicity syndrome; MLL, mixed-lineage leukemia; MRD, minimal residual disease.
All 40 patients with R/R CNS disease were put into 2 separate cohorts to evaluate outcomes based on specific patient scenarios and important questions related to treating CNS disease.