Table I.

Incidence and Management of Late toxicities with CAR T-cell Therapy

Late Effects	Incidence	Management
Hematological
Prolonged Cytopenias	Anemia: 17–53% Thrombocytopenia: 16–41% Neutropenia: 3–53% ALL>NHL1–3,13,25,26	Blood product transfusion G-CSF support Thrombopoietin receptor agonists Prophylactic anti-bacterial and antifungal agents in patients with prolonged neutropenia
Hypogammaglobulinemia	23–100%1–3,13,15	Immunoglobulin replacement [IVIG or subcutaneous formulation]: Dosing every 3–4 weeks at 400–600 mg/kg body weight to maintain IgG trough level of ≥400 mg/dl and continuing until B-cell recovery with spontaneous immunoglobulin production
Neurologic
Neurologic and Psychiatric Events	4–9%W3,31	Supportive care Management directed to specific adverse events Role of steroids or anti-IL6 antibody unclear
Immune-related Adverse Events	8%13	First-line: Corticosteroids Consider additional immunosuppression if unresponsive to steroids Multidisciplinary collaboration Refer to NCCN guidelines for managing IRAEs
Second Cancers	1–15%2,13 Hematologic Cancers: 1–6% Solid Cancers: 0–9%	Cancer surveillance[Follow HCT-specific guidelines] Age appropriate cancer screening among patients in CR Rule out therapy-related myeloid neoplasms in patients with prolonged cytopenias
Late Infections	8–61%1,3,13,31	Immunoglobulin replacement G-CSF support [GM-CSF should be avoided] Prophylactic antibiotic Follow HCT-specific guidelines for vaccination
Cardiac Toxicities	Troponin elevation: 54% Decreased LVEF: 28% CV deaths: 12%52	Consider monitoring serum troponin after CAR T-cell therapy based on clinical judgement Consider early administration of tocilizumab after CRS onset

Abbreviations: ALL: Acute Lymphoblastic Leukemia. NHL: Non-Hodgkin Lymphoma. IVIG: Intravenous Immunoglobulin. CR: Complete Response.

Note: Management recommendations in this table are based on current state of evidence and expert opinion.