Clinical, biochemical and correlative analysis for patient 2. (A) Time course of events following CAR T-cell infusion, including adverse events, infectious complications, stem cell infusion, and trends of inflammatory markers and blood counts. (B) Therapeutic strategies employed for managing CAR T-cell–related toxicities. For the first episode of CRS, immune effector cell–associated neurotoxicity syndrome (ICANS), and IEC-HS, the patient received 2 doses of tocilizumab (8 mg/kg), followed by methylprednisolone (1 g), and a dexamethasone taper for ICANS, along with anakinra (100 mg every 6 hours) for 5 days, which was then tapered over 10 days. For recurrent IEC-HS, treatment was initially started with dexamethasone (10 mg every 6 hours) but was later escalated to methylprednisolone (1 g) because of a refractory clinical course. Anakinra (100 mg every 6 hours) and ruxolitinib (5 mg twice daily) were also added. In addition, the patient received intrathecal methotrexate (12 mg) and IV cyclophosphamide (500 mg/m2) 2 weeks before death. (C) Immunophenotyping of peripheral blood, showing CAR T-cell expansion, gated on CD3+ viable lymphocytes. (D) H&E staining of BM on day 28 (after cilta-cel infusion) (left), demonstrating hypocellular marrow (<10%) with extensive marrow fibrosis in trichrome staining (right). ALC, absolute lymphocyte count; ANC, absolute neutrophil count; CRP, C-reactive protein; VII N palsy, seventh cranial nerve palsy.
