Recommendations for diagnostic workup and treatment of CAR T-cell–related myelopathy
| . | We recommend . | To be considered . | Investigational . |
|---|---|---|---|
| Diagnosis | Brain and spine MRI with and without contrast Evaluation for constipation and urinary retention with bladder scan Early consultations with neurology and infectious disease specialists If no contraindication, lumbar puncture with opening pressure measurement and CSF analysis (biochemistry, cell count, cytology, flow cytometry, and oligoclonal bands) Infectious workup on CSF, including cultures and NAT for HHV-6, CMV, VZV, HSV-1/2, JC-virus, EBV, adenovirus, and enteroviruses Infectious workup on peripheral blood, including cultures, QuantiFERON, HIV and hepatitis testing, Treponema pallidum testing, NAT for HHV-6, EBV, adenovirus, and CMV Serologic investigation, including vitamin B12, folate, methylmalonic acid, homocysteine, vitamin E, copper, ceruloplasmin, ferritin, C-reactive protein, CBC, LDH, liver enzymes, bilirubin, INR, PTT, creatinine, and extended electrolytes | Autoantibody testing (onconeural, AQP4, MOG antibodies) in CSF if previous exposure to ICIs and as per neurology for other patients Extended infectious workup on CSF and peripheral blood guided by an infectious disease specialist Serologic investigations if suspicion of IEC-HS, including triglycerides, fibrinogen, lactate, and soluble IL-2 receptor-α. Other serologic test: thiamine level Serology analysis for rheumatoid disease and NMO, including ANA, anti-Ro/La, anti-AQP4 testing, and other autoantibodies as guided by the clinical picture Electrodiagnostic studies | Extended cytokine panel on peripheral blood and/or CSF Lymphocytes subsets in peripheral blood and/or CSF Measurement of CAR T-cell expansion in peripheral blood and/or CSF |
| Treatment | High-dose steroids: methylprednisolone 1 g IV daily for 3-5 d with a slow taper depending on response and etiologic workup Avoidance of tocilizumab if no concurrent CRS If an infectious cause is identified: targeted antimicrobial therapy Medication review and avoidance of neurotoxic agents Correction of deficiencies in essential micronutrients Correction of hyponatremia Early rehabilitation | Empirical thiamine repletion: for example, 500 mg every 8 h for 72 h, followed by daily maintenance supplementation Empirical treatment for HHV-6 and CMV while awaiting results Other empirical infectious treatments if there are risk factors and if patient is not improving on initial steroid therapy IVIG 2 g/kg administered in divided doses per package insert, or plasmapheresis if previous exposure to ICIs. IVIG could be considered for other patients if refractory to initial treatment with pulse dose steroids Anakinra if refractory to initial management | Siltuximab Emapalumab Canakinumab Basiliximab Ruxolitinib BTK inhibitors Other TKI Salvage therapy (etoposide, cyclophosphamide, alemtuzumab, and ATG) |
| . | We recommend . | To be considered . | Investigational . |
|---|---|---|---|
| Diagnosis | Brain and spine MRI with and without contrast Evaluation for constipation and urinary retention with bladder scan Early consultations with neurology and infectious disease specialists If no contraindication, lumbar puncture with opening pressure measurement and CSF analysis (biochemistry, cell count, cytology, flow cytometry, and oligoclonal bands) Infectious workup on CSF, including cultures and NAT for HHV-6, CMV, VZV, HSV-1/2, JC-virus, EBV, adenovirus, and enteroviruses Infectious workup on peripheral blood, including cultures, QuantiFERON, HIV and hepatitis testing, Treponema pallidum testing, NAT for HHV-6, EBV, adenovirus, and CMV Serologic investigation, including vitamin B12, folate, methylmalonic acid, homocysteine, vitamin E, copper, ceruloplasmin, ferritin, C-reactive protein, CBC, LDH, liver enzymes, bilirubin, INR, PTT, creatinine, and extended electrolytes | Autoantibody testing (onconeural, AQP4, MOG antibodies) in CSF if previous exposure to ICIs and as per neurology for other patients Extended infectious workup on CSF and peripheral blood guided by an infectious disease specialist Serologic investigations if suspicion of IEC-HS, including triglycerides, fibrinogen, lactate, and soluble IL-2 receptor-α. Other serologic test: thiamine level Serology analysis for rheumatoid disease and NMO, including ANA, anti-Ro/La, anti-AQP4 testing, and other autoantibodies as guided by the clinical picture Electrodiagnostic studies | Extended cytokine panel on peripheral blood and/or CSF Lymphocytes subsets in peripheral blood and/or CSF Measurement of CAR T-cell expansion in peripheral blood and/or CSF |
| Treatment | High-dose steroids: methylprednisolone 1 g IV daily for 3-5 d with a slow taper depending on response and etiologic workup Avoidance of tocilizumab if no concurrent CRS If an infectious cause is identified: targeted antimicrobial therapy Medication review and avoidance of neurotoxic agents Correction of deficiencies in essential micronutrients Correction of hyponatremia Early rehabilitation | Empirical thiamine repletion: for example, 500 mg every 8 h for 72 h, followed by daily maintenance supplementation Empirical treatment for HHV-6 and CMV while awaiting results Other empirical infectious treatments if there are risk factors and if patient is not improving on initial steroid therapy IVIG 2 g/kg administered in divided doses per package insert, or plasmapheresis if previous exposure to ICIs. IVIG could be considered for other patients if refractory to initial treatment with pulse dose steroids Anakinra if refractory to initial management | Siltuximab Emapalumab Canakinumab Basiliximab Ruxolitinib BTK inhibitors Other TKI Salvage therapy (etoposide, cyclophosphamide, alemtuzumab, and ATG) |
ANA, antinuclear antibody; AQP4, aquaporin-4; ATG, antithymocyte globulin; BTK, Bruton’s tyrosine kinase; CBC, complete blood count; HSV-1/2, herpes simplex virus 1/2; INR, international normalized ratio; LDH, lactate dehydrogenase; MOG, myelin oligodendrocyte glycoprotein; NAT, nucleic acid testing; NMO, neuromyelitis optica; PTT, partial thromboplastin time; TKI, tyrosine kinase inhibitor; VZV, varicella-zoster virus.