LAUSR

Immunotherapy is a major breakthrough in cancer management [1]. Currently, immunotherapy with either autologous T cells engineered to express a chimeric antigen receptor (CAR) or with T-cell-engaging bispecific antibody designed to link CD3+ T-cells and tumour cells expressing a given antigen (CD19 or CD20 for instance) is being evaluated for the treatment of many cancers [2, 3]. However, both CAR-T cells and T-cell-engaging bispecific antibodies have been associated with serious adverse effects, known as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), that can be life-threatening [3–5]. We report herein the case of a 79-year-old patient treated in the haematology ward of our academic hospital for an aggressive diffuse large B-cell lymphoma refractory to several lines of therapy. The patient was treated with a Tcell-engaging bispecific antibody linking CD3+ T cells to CD20+ malignant B cells. The patient had no major comorbidity and was fit (ECOG performance status of 0) but presented with bulky disease involving many abdominal lymph nodes (Ann Arbor stage IV). Unfortunately, a few hours after infusion he developed a grade-2 CRS that rapidly deteriorated to grade 4 and needed intensive care unit (ICU) admission for appropriate management. Infection was ruled out by blood and bronchoalveolar lavage culture for both bacteria and fungi, and viral PCR analysis (HHV6, ADV, EBV, CMV) of bronchoalveolar lavage, peripheral blood, and bone marrow aspirate; both (1-3)-beta-D-glucan and galactomannan biomarkers were within the normal range. Antibiotics and anti-fungal therapy (piperacillin plus tazobactam, vancomycin, and caspofungin) were initiated without waiting for results of analysis that were later found to be all negative. The patient received three injections of tocilizumab 8 mg/kg over a 24-h period and 10 mg dexamethasone 4 times a day [5]. He also received 8000 mL of balanced crystalloids during the same 24-h period. Norepinephrine was rapidly required and infusion rate rose dramatically (up to 1.5 μg/kg/min) despite tocilizumab and corticosteroids. Intubation with mechanical ventilation and renal replacement therapy (RRT) was rapidly initiated. Because of the worsening condition despite optimal management of CRS, we decided to use a cytokine adsorption device; CytoSorb® (CytoSorbents corporation, South Brunswick township, NJ, USA). This was associated with a continuous venovenous haemodialysis using regional citrate anticoagulation. Blood flow was set to 100 mL/min and dialysate flow to 2000 mL/h for both sequences. Citrate and calcium infusion rates were adapted following our local protocol. Six hours after initiation of the first CytoSorb® sequence (each consecutive one lasting 24 h), norepinephrine was reduced and subsequently fully discontinued after the second sequence. No more fluid expansion was needed after the initiation of CytoSorb® epuration (Fig. 1). Two hours after CytoSorb® initiation, IL-6 was lowered by 75% (from 11813 to 2941 pg/mL) and IL-10 by 63% (from 170 to 63 pg/mL); 24 h after the beginning of epuration, IL-6 decreased from 11813 to 841 pg/mL and IL-10 decreased from 170 to 15 pg/mL (Fig. 2). * Florent Wallet [email protected]