Patient and treatment characteristics
| ID . | Sex . | Age, y . | Disease pathology . | Prior lines of therapy (most recent response) . | Site of CNS disease (maximal dimension) . | Systemic isease? . | Maximum CRS/NT (Lee 20144 ) . | Maximum CRS/NT (ASTCT 20196 ) . | Required treatment for CRS/NT? . | Concomitant maintenance during CAR T-cell therapy? . | D+28 response . | Subsequent follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 43 | DLBCL, GCB like | R-CHOP + HD-MTX with CNS relapse | Cerebral peduncles and midbrain, as well as the 3rd and 7/8th cranial nerves. | No | Grade 1 CRS. Grade 1 NT (headache). | Grade 1 CRS. No NT.* | No | Ibrutinib | Deceased, disease progression | |
| CYVE with relapse | ||||||||||||
| R-cytarabine with relapse | ||||||||||||
| Ibrutinib maintenance (progressive disease) | ||||||||||||
| 2 | F | 64 | HGBCL | DA-EPOCH-R + IT-MTX | CSF intermittently positive | Right lateral psoas (1.8 cm) | No CRS. No NT. | No CRS. No NT.* | No | None | CR, CSF (−) | Systemic relapse at D+90, CNS (−). RT to focal relapse with resolution on D+180 scans. No additional CNS-directed therapy. |
| HDC-ASCT with systemic/CNS relapse | ||||||||||||
| GemOx + HD-MTX | ||||||||||||
| RIC MUD with systemic/CNS relapse | ||||||||||||
| Cessation of immunosuppression & monthly IT-MTX maintenance for 6 mo (CNS: stable disease; systemic: progressive disease) | ||||||||||||
| 3 | M | 61 | DLBCL, GCB like | R-CHOP with CNS relapse | CSF+, ventral nerve root from T12 to L2, L1/L5 vertebral involvement | No | Grade 1 CRS. Grade 1 NT (neuropathy). | Grade 1 CRS. No NT.* | No | None | PR, CSF (−) | CR at D+180 |
| HD-MTX with CNS relapse | ||||||||||||
| CYVE with CNS relapse | ||||||||||||
| Twice weekly IT-MTX maintenance (PR) | ||||||||||||
| 4 | F | 56 | DLBCL, GCB like | R-CHOP with systemic relapse | Right superior frontal gyrus (1.4 cm) | Hepatic (4.5 cm) & mesenteric lymphadenopathy | Grade 1 CRS. No NT. | Grade 1 CRS. No NT.* | No | Ibrutinib | PD | WBI, lenalidomide |
| R-ICE with systemic/CNS relapse | ||||||||||||
| R-ibrutinib (CNS & systemic: PR) | ||||||||||||
| 5 | M | 24 | HGBCL | Modified McGrath regimen, CNS relapse | Left cerebellar (0.7 cm) and diffuse leptomeningeal involvement | No | Grade 1 CRS. NT.† | Grade 1 CRS. NT.† | No | Ibrutinib/steroids | Deceased; disease progression. | |
| HD-MTX with CNS progression | ||||||||||||
| CYVE with CNS progression | ||||||||||||
| IT cytarabine/MTX with CNS progression | ||||||||||||
| Pemetrexed with CNS progression | ||||||||||||
| Ibrutinib (progressive disease) | ||||||||||||
| 6 | M | 44 | DLBCL, GCB like | R-CHOP with systemic/CNS relapse | CSF+, intradural extramedullary nodule adjacent to the conus at L1 (2.5 cm). | No | Grade 1 CRS. No NT. | Grade 1 CRS. No NT. | No | None | PD, prior sites resolved, new PET-avid lesion, CSF+. | Ibrutinib maintenance, RT to residual disease. |
| HD-MTX–R with CNS progression | ||||||||||||
| CYVE with CNS progression | ||||||||||||
| Ibrutinib with CNS progression | ||||||||||||
| REVLIMID with CNS progression | ||||||||||||
| HiDAC (PR) | ||||||||||||
| 7 | M | 17 | PMBCL | DA-EPOCH-R with CNS relapse | Multiple sites, including right basal ganglia (2.3 cm), septum pellucidum and corpus callosum (2.1 cm), 9th-11th cranial nerves. | No | Grade 1 CRS. No NT. | Grade 1 CRS. No NT.* | No | None | PR | Ongoing response at D+90, decreased avidity of PET/MRI to adjacent brain parenchyma. |
| HD-MTX with CNS progression | ||||||||||||
| HiDAC with CNS progression | ||||||||||||
| Brentuximab and CYVE with partial response | ||||||||||||
| RT + pembro with CNS progression, craniospinal axis irradiation (PR) | ||||||||||||
| 8 | F | 79 | DLBCL, non-GCB | R-CHOP + HD-MTX with consolidative XRT with CNS relapse | Left Meckel’s cave and temporal lobe (5.0 cm) | No | Grade 1 CRS. Grade 1 NT (tremors). | Grade 1 CRS. No NT.* | No | None | CR | Ongoing response at D+90 |
| HD-MTX with progression | ||||||||||||
| R-HiDAC with PR | ||||||||||||
| Ibrutinib maintenance eventually held for rash (PD) |
| ID . | Sex . | Age, y . | Disease pathology . | Prior lines of therapy (most recent response) . | Site of CNS disease (maximal dimension) . | Systemic isease? . | Maximum CRS/NT (Lee 20144 ) . | Maximum CRS/NT (ASTCT 20196 ) . | Required treatment for CRS/NT? . | Concomitant maintenance during CAR T-cell therapy? . | D+28 response . | Subsequent follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 43 | DLBCL, GCB like | R-CHOP + HD-MTX with CNS relapse | Cerebral peduncles and midbrain, as well as the 3rd and 7/8th cranial nerves. | No | Grade 1 CRS. Grade 1 NT (headache). | Grade 1 CRS. No NT.* | No | Ibrutinib | Deceased, disease progression | |
| CYVE with relapse | ||||||||||||
| R-cytarabine with relapse | ||||||||||||
| Ibrutinib maintenance (progressive disease) | ||||||||||||
| 2 | F | 64 | HGBCL | DA-EPOCH-R + IT-MTX | CSF intermittently positive | Right lateral psoas (1.8 cm) | No CRS. No NT. | No CRS. No NT.* | No | None | CR, CSF (−) | Systemic relapse at D+90, CNS (−). RT to focal relapse with resolution on D+180 scans. No additional CNS-directed therapy. |
| HDC-ASCT with systemic/CNS relapse | ||||||||||||
| GemOx + HD-MTX | ||||||||||||
| RIC MUD with systemic/CNS relapse | ||||||||||||
| Cessation of immunosuppression & monthly IT-MTX maintenance for 6 mo (CNS: stable disease; systemic: progressive disease) | ||||||||||||
| 3 | M | 61 | DLBCL, GCB like | R-CHOP with CNS relapse | CSF+, ventral nerve root from T12 to L2, L1/L5 vertebral involvement | No | Grade 1 CRS. Grade 1 NT (neuropathy). | Grade 1 CRS. No NT.* | No | None | PR, CSF (−) | CR at D+180 |
| HD-MTX with CNS relapse | ||||||||||||
| CYVE with CNS relapse | ||||||||||||
| Twice weekly IT-MTX maintenance (PR) | ||||||||||||
| 4 | F | 56 | DLBCL, GCB like | R-CHOP with systemic relapse | Right superior frontal gyrus (1.4 cm) | Hepatic (4.5 cm) & mesenteric lymphadenopathy | Grade 1 CRS. No NT. | Grade 1 CRS. No NT.* | No | Ibrutinib | PD | WBI, lenalidomide |
| R-ICE with systemic/CNS relapse | ||||||||||||
| R-ibrutinib (CNS & systemic: PR) | ||||||||||||
| 5 | M | 24 | HGBCL | Modified McGrath regimen, CNS relapse | Left cerebellar (0.7 cm) and diffuse leptomeningeal involvement | No | Grade 1 CRS. NT.† | Grade 1 CRS. NT.† | No | Ibrutinib/steroids | Deceased; disease progression. | |
| HD-MTX with CNS progression | ||||||||||||
| CYVE with CNS progression | ||||||||||||
| IT cytarabine/MTX with CNS progression | ||||||||||||
| Pemetrexed with CNS progression | ||||||||||||
| Ibrutinib (progressive disease) | ||||||||||||
| 6 | M | 44 | DLBCL, GCB like | R-CHOP with systemic/CNS relapse | CSF+, intradural extramedullary nodule adjacent to the conus at L1 (2.5 cm). | No | Grade 1 CRS. No NT. | Grade 1 CRS. No NT. | No | None | PD, prior sites resolved, new PET-avid lesion, CSF+. | Ibrutinib maintenance, RT to residual disease. |
| HD-MTX–R with CNS progression | ||||||||||||
| CYVE with CNS progression | ||||||||||||
| Ibrutinib with CNS progression | ||||||||||||
| REVLIMID with CNS progression | ||||||||||||
| HiDAC (PR) | ||||||||||||
| 7 | M | 17 | PMBCL | DA-EPOCH-R with CNS relapse | Multiple sites, including right basal ganglia (2.3 cm), septum pellucidum and corpus callosum (2.1 cm), 9th-11th cranial nerves. | No | Grade 1 CRS. No NT. | Grade 1 CRS. No NT.* | No | None | PR | Ongoing response at D+90, decreased avidity of PET/MRI to adjacent brain parenchyma. |
| HD-MTX with CNS progression | ||||||||||||
| HiDAC with CNS progression | ||||||||||||
| Brentuximab and CYVE with partial response | ||||||||||||
| RT + pembro with CNS progression, craniospinal axis irradiation (PR) | ||||||||||||
| 8 | F | 79 | DLBCL, non-GCB | R-CHOP + HD-MTX with consolidative XRT with CNS relapse | Left Meckel’s cave and temporal lobe (5.0 cm) | No | Grade 1 CRS. Grade 1 NT (tremors). | Grade 1 CRS. No NT.* | No | None | CR | Ongoing response at D+90 |
| HD-MTX with progression | ||||||||||||
| R-HiDAC with PR | ||||||||||||
| Ibrutinib maintenance eventually held for rash (PD) |
ASTCT, American Society for Transplantation and Cellular Therapy; CR, complete response; CSF, cerebral spinal fluid; CYVE, cytarabine/etoposide; DA-EPOCH-R, dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; F, female; GCB, germinal center B cell; GemOx, gemcitabine/oxaliplatin; HDC-ASCT, high-dose chemotherapy + autologous stem cell transplant; HD-MTX, high-dose methotrexate; HiDAC, high-dose cytarabine; IT, intrathecal; IT-MTX, intrathecal methotrexate; M, male; MTX, methotrexate; MUD, matched unrelated donor; PD, progressive disease; PET, positron emission tomography; PMBCL, primary mediastinal B-cell lymphoma; PR, partial response; R, rituxan; R-CHOP, rituxan/cyclophosphamide/doxorubicin/vincristine/prednisone; RIC, reduced intensity conditioning; R-ICE, rituxan/ifosfamide/carboplatin/etoposide; RT, radiotherapy; WBI, whole-brain irradiation; XRT, radiation therapy.
Immune Effector Cell-Associated Encephalopathy score not able to be calculated retrospectively.
Not evaluable because of disease progression.