Search

Background: Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy. Methods: This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018–2022 within 3 months after CAR-T therapy. Results: Among 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0–7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2–6] and 39 [30–48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3–4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3–4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1–4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU. Conclusion: ICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3–4 toxicities, and half of patients being alive and in complete remission at one year. [ABSTRACT FROM AUTHOR]

Background: Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are well-documented toxicities of CAR T-cell therapy. To mitigate excessive toxicity, our center has formulated treatment protocols (early vs. standard) for timely management of CRS and ICANS with tocilizumab and/or corticosteroids. Methods: This retrospective, single-center analysis included patients treated with CAR T-cell therapy. The goal was to describe the association of two management protocols with toxicity and efficacy outcomes. Results: Fifty-five percent of the 40 patients assigned to early management, out of which 5% and 9% developed grade 3+ CRS and ICANS, respectively. Seventy-seven percent and 41% of these patients received tocilizumab and corticosteroids, respectively. Forty-five percent of patients were stratified as standard management, out of which 0% and 11% developed grade 3+ CRS and ICANS, respectively. Seventeen percent and 28% of these patients received tocilizumab and corticosteroids, respectively. The day +90 overall response rate (ORR) for all patients was 63%, with an ORR of 89% for those managed per early management versus 50% for those managed per standard protocol. Conclusion: Early use of tocilizumab and corticosteroids is effective in preventing excessive CAR-T-related toxicities with no negative impact on efficacy. [ABSTRACT FROM AUTHOR]

Cytokine release syndrome (CRS) is a systemic inflammatory condition caused by an excessive immune response and cytokine overproduction. CRS is a life-threatening condition that is often associated with chimeric antigen receptor T-cell therapy. Despite the increased use of immune checkpoint inhibitors (ICIs), ICI-induced CRS remains rare. The present study describes a case of CRS that occurred after the administration of ICIs for recurrent adenocarcinoma of the uterine cervix. A 49-year-old woman received paclitaxel, carboplatin and pembrolizumab for recurrent cervical adenocarcinoma. On day 27 of the third cycle, the patient was admitted with a fever and suspected pyelonephritis. The following day, hypotension, upper respiratory symptoms and myalgia of the extremities were noted, and the left ventricular ejection fraction (LVEF) was decreased to 20%. Multiorgan failure (MOF) occurred, and the patient received ventilator support and continuous hemodiafiltration. Rhabdomyolysis, pancreatitis, erythema multiforme and enteritis were observed. CRS was diagnosed based on elevated ferritin and IL-6 levels. Steroid pulse therapy was administered; however, the MOF did not improve and the anti-IL-6-receptor monoclonal antibody tocilizumab (TOC) was administered. Subsequently, the LVEF improved to 50%, and the patient was removed from the ventilator on day 4 and from the continuous hemodiafiltration unit on day 6 after TOC administration. The patient was discharged on day 21. In conclusion, considering that ICI-induced CRS is a rare but severe complication, fever and other systemic conditions following ICI administration should be monitored. [ABSTRACT FROM AUTHOR]

• CRS is the most prevalent complication of CAR-T therapy. • Therapeutic plasma exchange can be a valuable and safe treatment for severe CRS caused by CAR-T cell infusion. • The temperature and inflammatory markers exhibited a significant reduction following therapeutic plasma exchange treatment. The chimeric antigen receptor T (CAR-T) cell therapy significantly enhances the prognosis of various hematologic malignancies; however, the systemic expansion of CAR-T cells also gives rise to severe cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Despite the successful application of corticosteroids and tocilizumab in alleviating severe CRS in most patients, there are still individuals who experience life-threatening CRS without responding to the aforementioned therapies. In our retrospective cohort, we conducted an analysis of clinical and laboratory parameters, including inflammatory cytokines, in 17 patients from three centers who underwent therapeutic plasma exchange (TPE) for refractory CRS with or without ICANS following CAR-T products treatment. Our findings demonstrate a significant improvement in both clinical symptoms and laboratory parameters subsequent to TPE treatment. The rapid decrease in temperature and levels of inflammatory indexes indicates the remarkable scavenging efficacy of TPE against cytokine storm following CAR-T therapy. In conclusion, TPE may serve as a valuable and safe adjunct to corticosteroids and tocilizumab in the management of severe CRS resulting from CAR-T cell infusion. We eagerly await further prospective studies to validate this finding. [ABSTRACT FROM AUTHOR]