Post-transplant lymphoproliferative disorder (PTLD), classical Hodgkin lymphoma
Modified Ann Arbor classification: stage IIB
- December 2024: First diagnosis of classical Hodgkin lymphoma (Epstein–Barr virus negative)
- December 2024 – April 2025: Treatment with brentuximab vedotin combined with doxorubicin, bleomycin, vinblastine, and dacarbazine; initial remission followed by relapse in May 2025
- May 2025: Therapy switched to pembrolizumab
Approximately four hours after the first dose: severe immune effector cell-associated neurotoxicity syndrome (ICANS) requiring intermediate and intensive care; good response to high-dose methylprednisolone.
Discussion in the interdisciplinary Toxicity Board: Due to the favorable tumor response to pembrolizumab and the effective management of ICANS with steroids, rechallenge with pembrolizumab was considered.
- June 2025: Pembrolizumab restarted under steroid coverage; complete remission on PET-CT
- July 2025: Detection of partial osseous relapse; clinically stable
- August 2025: Fourth cycle of pembrolizumab well tolerated
Rechallenge with immune checkpoint inhibitors (ICIs) after an immune-related adverse event (irAE) carries an approximately one-third risk of recurrence of the immunemediated side effect. ICANS is a neurotoxic syndrome characterized by encephalopathy, speech disturbances, seizures, decreased vigilance, and cerebral edema. Pathophysiologically, cytokine-mediated blood-brain barrier disruption plays a central role. ICANS frequently occurs after chimeric antigen receptor T-cell (CAR-T) therapies, with significantly higher incidence and severity. In contrast, fulminant ICANS is extremely rare with ICIs but has been occasionally reported and requires prompt, interdisciplinary management.
- Zhao, Q., et al. (2021). Safety and Efficacy of the Rechallenge of Immune Checkpoint Inhibitors After Immune-Related Adverse Events: A Systematic Review and Meta-Analysis. Frontiers in Immunology, 12, 747267.
- Genoud, V., & Migliorini, D. (2023). Novel pathophysiological insights into CAR-T cell-associated neurotoxicity. Frontiers in Immunology, 14, 1150532