CNS disease characteristics and treatments
| Characteristic . | Value (n = 10) . | % . |
|---|---|---|
| CNS disease | ||
| Brain/cranial nerve involvement only | 4 | 40 |
| Both brain/cranial nerve and spinal cord involvement | 6 | 60 |
| MRI abnormalities at diagnosis of CNS disease | ||
| Yes | 10 | 100 |
| No | 0 | 0 |
| CSF abnormal at diagnosis of CNS disease | ||
| Yes | 4 | 40 |
| No | 2 | 20 |
| N/A | 4 | 40 |
| No. of days between CNS disease diagnosis to CAR T-cell therapy | ||
| ≤30 d, n, median (range) | 2, 26 (21-30) | 20 |
| 31-60 d, n, median (range) | 3, 42 (34-56) | 30 |
| >300 d, n, median (range) | 3, 587 (344-710) | 30 |
| Diagnosed soon after CAR T-cell therapy, n, median (range) | 2∗ | 20 |
| CNS-directed therapy | ||
| Part of bridging therapy before CAR T-cell therapy† | ||
| RT (brain and/or spine) | 2 | 20 |
| IT chemotherapy | 1 | 10 |
| RT + IT chemotherapy | 3 | 30 |
| Surgery + RT | 1 | 10 |
| Post-CAR T-cell therapy | ||
| RT after CAR T-cell therapy | 2 | 20 |
| None (due to recent DCEP chemotherapy) | 1 | 10 |
| No. of days between last RT session and CAR T-cell infusion | ||
| Median (range) | 14.5 (9-39) | |
| Systemic bridging therapy‡ | ||
| mCBAD | 1 | 10 |
| KCd (±RT) | 2 | 20 |
| Vd (±revlimid ± RT) | 2 | 20 |
| DCEP (±RT) | 2 | 20 |
| PXd (+RT) | 1 | 10 |
| VD-CE (+IT chemotherapy and RT) | 1 | 10 |
| Dara-Pom-Dex+Seli (+IT chemotherapy and RT) | 1 | 10 |
| Treated vs untreated known CNS disease at time of LDC (n = 8)§ | ||
| Treated | 7/8 | 87.5 |
| Untreated | 1/8 | 12.5 |
| CAR T-cell product | ||
| Ide-cel | 6 | 60 |
| Cilta-cel | 4 | 40 |
| CAR T-cell dose | ||
| Ide-cel median (range) million cells | 427 (154-447) | |
| Cilta-cel | ||
| Median (range) dose, ×106 CAR+ per kg | 0.7 (0.6-0.7) | |
| Median (range) million cells | 54 (47-61) | |
| CAR T-cell manufacturing | ||
| Out-of-specification products | 0 | 0 |
| Successful manufacturing on first attempt | 9 | 90 |
| Successful manufacturing on second attempt | 1 | 10 |
| Lymphodepletion received before CAR T-cell therapy | ||
| Fludarabine and cyclophosphamide | 10 | 100 |
| Treatments after CAR T-cell therapy | ||
| CNS-directed RT | 2 | 20 |
| For 2 patients with CNS disease diagnosed after CAR T-cell therapy | ||
| In one of them this was followed by Elo-Pom-Dex, VD-AC, and teclistamab | ||
| Pomalidomide-based therapy | ||
| Daratumumab-pomalidomide-dexamethasone | 1 | 10 |
| Selinexor-pomalidomide-dexamethasone ± IT chemotherapy ± RT | 2 | 20 |
| Isatuximab-carfilzomib-dexamethasone | 2 | 20 |
| BCMA-directed bispecific therapy (teclistamab) | 1 | 10 |
| None or N/A | 2 | 20 |
| Characteristic . | Value (n = 10) . | % . |
|---|---|---|
| CNS disease | ||
| Brain/cranial nerve involvement only | 4 | 40 |
| Both brain/cranial nerve and spinal cord involvement | 6 | 60 |
| MRI abnormalities at diagnosis of CNS disease | ||
| Yes | 10 | 100 |
| No | 0 | 0 |
| CSF abnormal at diagnosis of CNS disease | ||
| Yes | 4 | 40 |
| No | 2 | 20 |
| N/A | 4 | 40 |
| No. of days between CNS disease diagnosis to CAR T-cell therapy | ||
| ≤30 d, n, median (range) | 2, 26 (21-30) | 20 |
| 31-60 d, n, median (range) | 3, 42 (34-56) | 30 |
| >300 d, n, median (range) | 3, 587 (344-710) | 30 |
| Diagnosed soon after CAR T-cell therapy, n, median (range) | 2∗ | 20 |
| CNS-directed therapy | ||
| Part of bridging therapy before CAR T-cell therapy† | ||
| RT (brain and/or spine) | 2 | 20 |
| IT chemotherapy | 1 | 10 |
| RT + IT chemotherapy | 3 | 30 |
| Surgery + RT | 1 | 10 |
| Post-CAR T-cell therapy | ||
| RT after CAR T-cell therapy | 2 | 20 |
| None (due to recent DCEP chemotherapy) | 1 | 10 |
| No. of days between last RT session and CAR T-cell infusion | ||
| Median (range) | 14.5 (9-39) | |
| Systemic bridging therapy‡ | ||
| mCBAD | 1 | 10 |
| KCd (±RT) | 2 | 20 |
| Vd (±revlimid ± RT) | 2 | 20 |
| DCEP (±RT) | 2 | 20 |
| PXd (+RT) | 1 | 10 |
| VD-CE (+IT chemotherapy and RT) | 1 | 10 |
| Dara-Pom-Dex+Seli (+IT chemotherapy and RT) | 1 | 10 |
| Treated vs untreated known CNS disease at time of LDC (n = 8)§ | ||
| Treated | 7/8 | 87.5 |
| Untreated | 1/8 | 12.5 |
| CAR T-cell product | ||
| Ide-cel | 6 | 60 |
| Cilta-cel | 4 | 40 |
| CAR T-cell dose | ||
| Ide-cel median (range) million cells | 427 (154-447) | |
| Cilta-cel | ||
| Median (range) dose, ×106 CAR+ per kg | 0.7 (0.6-0.7) | |
| Median (range) million cells | 54 (47-61) | |
| CAR T-cell manufacturing | ||
| Out-of-specification products | 0 | 0 |
| Successful manufacturing on first attempt | 9 | 90 |
| Successful manufacturing on second attempt | 1 | 10 |
| Lymphodepletion received before CAR T-cell therapy | ||
| Fludarabine and cyclophosphamide | 10 | 100 |
| Treatments after CAR T-cell therapy | ||
| CNS-directed RT | 2 | 20 |
| For 2 patients with CNS disease diagnosed after CAR T-cell therapy | ||
| In one of them this was followed by Elo-Pom-Dex, VD-AC, and teclistamab | ||
| Pomalidomide-based therapy | ||
| Daratumumab-pomalidomide-dexamethasone | 1 | 10 |
| Selinexor-pomalidomide-dexamethasone ± IT chemotherapy ± RT | 2 | 20 |
| Isatuximab-carfilzomib-dexamethasone | 2 | 20 |
| BCMA-directed bispecific therapy (teclistamab) | 1 | 10 |
| None or N/A | 2 | 20 |
Dara PXd, Daratumumab Pomalidomide Selinexor Dexamethasone; Dara-Pom-Dex+Seli; Daratumumab, Pomalidomide, Dexamethasone, Selinexor; DCEP, dexamethasone, cyclophosphamide, etoposide, and cisplatin; Elo-Pom-Dex, Elotuzumab, Pomalidomide, Dexamethasone; KCd, carfilzomib cyclophosphamide dexamethasone; LDC, lymphodepleting chemotherapy; mCBAD, modified dosing cyclophosphamide bortezomib doxorubicin dexamethasone; N/A, not available; PXd, pomalidomide selinexor dexamethasone; RT, radiotherapy; Vd, bortezomib-dexamethasone; VD-AC, bortezomib-dexamethasone-doxorubicin-cyclophosphamide; VD-CE: bortezomib-dexamethasone-cyclophosphamide-etoposide.
For those 2 patients, CNS disease was diagnosed at days 11 and 14 after CAR T-cell therapy.
IT chemotherapy varied per institutional preference and included either IT cytarabine or IT methotrexate.
Systemic bridging therapies included mCBAD, KCd, Vd, DCEP, PXd, VD-CE, VD-AC, Dara-PXd, and RT.
Of 10 patients, 8 had known CNS disease before CAR T-cell therapy, of which 7 received CNS disease–directed therapy before CAR T-cell infusion. Two patients had their CNS disease discovered after CAR T-cell therapy so did not receive CNS-directed therapy before CAR T-cell therapy but did receive RT after CAR T-cell therapy.