Case Report: Successful use of emapalumab in adult B-cell acute lymphoblastic leukemia experiencing severe neurotoxicity and hemophagocytic lymphohistiocytosis-like features after CAR-T cell therapy

作者：Beatrice Manghisi, Giulia Cotilli, Marilena Fedele, Paola Perfetti, Elisabetta Terruzzi, Luisa Verga, Lorenza Maria Borin, Andrea Carrer, Monica Fumagalli, Maria Beatrice Ferrari, Alex Moretti, Roberto J. Rona, Annalisa Benini, Beatrice Vergnano, Giovanni Palumbo, Alessandra Zincone, Oscar Maglia, Chiara Mariadele Scollo, Carolina Steidl, Lorenzo Iovino, Adriana Balduzzi, Rocco Piazza, Carlo B Gambacorti-Passerini, Matteo Parma, Andrea Aroldi · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1563736 · 被引用次数：9 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、Acute Lymphoblastic Leukemia research

Chimeric antigen receptor (CAR)-T cell therapy is a powerful adoptive immunotherapy associated with significant toxicity, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). As CAR-T usage expands, hyperinflammatory toxicities resembling hemophagocytic lymphohistiocytosis (HLH) syndrome are increasingly recognized. Immune effector cell-associated HLH-like syndrome (IEC-HS) describes HLH-like symptoms attributable to CAR-T cell therapy, often presenting as CRS resolves. Treatments for IEC-HS are adapted from primary HLH, including corticosteroids, the recombinant human interleukin (IL)-1 receptor antagonist anakinra and the Janus Kinase inhibitor ruxolitinib. Emapalumab, an anti-IFN-γ antibody, is promising but underexplored in adult IEC-HS cases. We report an adult B-cell acute lymphoblastic leukemia (B-ALL) patient treated with brexucabtagene autoleucel (brexu-cel). The patient developed CRS, refractory neurotoxicity, and IEC-HS with worsening multiorgan failure and hyperinflammatory markers. Treatment included tocilizumab, high-dose corticosteroids, anakinra, siltuximab, and ruxolitinib. Despite aggressive management, hyperinflammation and neurotoxicity persisted. Emapalumab was initiated on day +11, resulting in normalization of the biochemical parameters and full neurological recovery by day +21. The patient recovered from IEC-HS and underwent allogeneic stem cell transplantation. This case highlights the role of e...