scholarly journals NCMP-24. PRE-INFUSION NEUROFILAMENT LIGHT CHAIN (NFL) LEVELS PREDICT THE DEVELOPMENT OF IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii127-ii128
Author(s):  
Omar Butt ◽  
Alice Zhou ◽  
Suzanne Schindler ◽  
Anne Fagan ◽  
John Dipersio ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Light Chain ◽  
Effector Cell ◽  
Immune Effector Cell ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Car T

Abstract Neurological side effects after chimeric antigen receptor-modified (CAR) T cell therapy are common and potentially devastating. Termed immune effector cell-associated neurotoxicity syndrome (ICANS), symptoms range from mild encephalopathy to diffuse cerebral edema. No predictive biomarkers exist to identify individuals at risk for developing ICANS. Serum neurofilament light chain (NfL) is a well-established marker of neural injury known to dynamically change in neuro-inflammatory disorders (e.g. multiple sclerosis). We hypothesized individuals undergoing CAR T cell therapy who ultimately developed ICANS would have early and sustained elevations in serum NfL. We performed a retrospective analysis of serum samples from 11 individuals treated with tisagenlecleucel or axicabtagene ciloleucel (mean age 61.3, 18% female, 27% ICANS, all with peak severity score 3). Most individuals had a longitudinal sampling at baseline, pre-infusion, post-transfusion day (PTD) 1, PTD 3, PTD 7, PTD 14, and PTD 30. Serum NfL were assayed using a Simoa HD-1/HD-X kit (QuanterixTM). We found that individuals who developed ICANS had early and sustained elevations in serum NfL levels at baseline (p = 0.0075), pre-infusion (p = 0.0172), and PTD 3 (p = 0.0026) and PTD 30 (p = 0.0066). All group comparisons survived multiple comparison testing using false-discovery rate (FDR). Receiver operating characteristic (ROC) curve classification by logistic regression of serum NfL revealed an area under the curve (AUC) of 1.0 with a cut-off of 44 pg/mL. No correlation was observed between NfL levels and age, sex, or history of central nervous system involvement of the underlying malignancy. In summary, we found serum NfL levels are a robust, early marker for the development of ICANS. Our findings suggest the risk of developing ICANS reflects pre-transfusion host-factors, permitting the screening well in advance of drug administration.

NCMP-20. PRE-INFUSION NEUROFILAMENT LIGHT CHAIN (NFL) LEVELS PREDICT THE DEVELOPMENT OF IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS) – A MULTICENTER RETROSPECTIVE STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi151-vi151
Author(s):  
Omar Butt ◽  
Alice Zhou ◽  
Kenneth Lee ◽  
Gregory Wu ◽  
Paolo Caimi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Effector Cell ◽  
Immune Effector Cell ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Car T ◽  
Post Infusion

Abstract BACKGROUND Neurological side effects after chimeric antigen receptor-modified (CAR) T cell therapy, termed immune effector cell-associated neurotoxicity syndrome (ICANS), are common and potentially devastating. We previously demonstrated that pre-infusion plasma neurofilament light chain (NfL), a well-established marker of neurodegeneration, may predict subsequent development of ICANS in a small, single-center cohort. This larger, retrospective multicenter study compares pre-infusion NfL to known post-infusion risk factors for developing ICANs including white blood cell (WBC) count, platelet count, C-reactive protein (CRP), fibrinogen, and ferritin levels. METHODS Inclusion criteria included available pre-infusion (up to 4 weeks prior to lymphodepletion) plasma from patients treated with a CAR T cell therapy (n = 30, 36% with ICANS, ASTCT consensus ICANS grade range 1-4). Exclusion criteria included confounding diagnoses known to elevate NfL levels (dementia, multiple sclerosis, recent stroke). Plasma NfL was assayed using a Simoa HD-1/HD-X kit (QuanterixTM). Post-infusion Day 3 or Day 5 WBC, Platelet, CRP, fibrinogen, and ferritin were obtained from the medical record. Group comparisons were done using log-rank tests with a Bonferroni-derived significance threshold, followed by receiver operating characteristic (ROC) curve classification. RESULTS Prior to infusion, individuals who ultimately developed ICANS had elevations in NfL ([87.6 v 29.4 pg/ml], p = 0.00004) with excellent classification (AUC 0.96), sensitivity (0.91) and specificity (0.95). Among known post-infusion risk factors, only post-infusion Day 3 ferritin (p = 0.004) and Day 5 ferritin (p = 0.003) differed between groups. Classification was inferior for both time points (Day 3 AUC = 0.87, specificity 0.71; Day 5 AUC 0.87, specificity 0.86). CONCLUSION Pre-infusion plasma NfL levels are a robust early marker for the development of ICANS that exceeds known post-infusion markers. Our findings suggest the risk of developing ICANS reflects pre-existing host-factors. Foreknowledge of ICANS development of may permit early, aggressive (preemptive or prophylaxis) ICANS-directed therapies, improving patient outcomes.

scholarly journals Immune effector cell–associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy for lymphoma: predictive biomarkers and clinical outcomes

2020 ◽  
Author(s):  
Noa G Holtzman ◽  
Hao Xie ◽  
Soren Bentzen ◽  
Vivek Kesari ◽  
Ali Bukhari ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Clinical Outcomes ◽  
Chimeric Antigen Receptor ◽  
Effector Cell ◽  
Immune Effector Cell ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has emerged as effective for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as immune effector cell–associated neurotoxicity syndrome (ICANS), is poorly understood. To better elucidate the clinical characteristics, treatment outcomes, and correlative biomarkers of ICANS, we review here a single-center analysis of ICANS after CAR T-cell therapy in R/R LBCL. Methods Patients (n = 45) with R/R LBCL treated with axicabtagene ciloleucel (axi-cel) were identified. Data regarding treatment course, clinical outcomes, and correlative studies were collected. Patients were monitored and graded for ICANS via CARTOX-10 scoring and Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, respectively. Results Twenty-five (56%) patients developed ICANS, 18 (72%) of whom had severe (CTCAE grades 3–4) ICANS. Median time to development of ICANS was 5 days (range, 3–11). Elevated pre-infusion (day 0 [D0]) fibrinogen (517 vs 403 mg/dL, upper limit of normal [ULN] 438 mg/dL, P = 0.01) and D0 lactate dehydrogenase (618 vs 506 units/L, ULN 618 units/L, P = 0.04) were associated with ICANS. A larger drop in fibrinogen was associated with ICANS (393 vs 200, P < 0.01). Development of ICANS of any grade had no effect on complete remission (CR), progression-free survival (PFS), or overall survival (OS). Duration and total dose of steroid treatment administered for ICANS did not influence CR, PFS, or OS. Conclusions ICANS after CAR-T with axi-cel for R/R LBCL was seen in about half of patients, the majority of which were high grade. Contrary to previous reports, neither development of ICANS nor its treatment were associated with inferior CR, PFS, or OS. The novel finding of high D0 fibrinogen level can identify patients at higher risk for ICANS.

scholarly journals Immune Effector Cell Associated Neurotoxicity (ICANS) in Pediatric and Young Adult Patients Following Chimeric Antigen Receptor (CAR) T-Cell Therapy: Can We Optimize Early Diagnosis?

2021 ◽  
Vol 11 ◽  
Author(s):  
Brandon Douglas Brown ◽  
Francesco Paolo Tambaro ◽  
Mira Kohorst ◽  
Linda Chi ◽  
Kris Michael Mahadeo ◽  
...  
Keyword(s):  
T Cell ◽  
Young Adult ◽  
Effector Cell ◽  
Adult Patients ◽  
Immune Effector Cell ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

The Cornell Assessment for Pediatric Delirium (CAPD) was first proposed by the Pediatric Acute Lung Injury and Sepsis Investigators Network-Stem Cell Transplantation and Cancer Immunotherapy Subgroup and MD Anderson CARTOX joint working committees, for detection of immune effector cell associated neurotoxicity (ICANS) in pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy. It was subsequently adopted by the American Society for Transplantation and Cellular Therapy. The utility of CAPD as a screening tool for early diagnosis of ICANS has not been fully characterized. We conducted a retrospective study of pediatric and young adult patients (n=15) receiving standard-of-care CAR T-cell products. Cytokine release syndrome (CRS) and ICANS occurred in 87% and 40% of patients, respectively. ICANS was associated with significantly higher peaks of serum ferritin. A change in CAPD from a prior baseline was noted in 60% of patients with ICANS, 24–72 h prior to diagnosis of ICANS. The median change from baseline to maximum CAPD score of patients who developed ICANS versus those who did not was 13 versus 3, respectively (p=0.0004). Changes in CAPD score from baseline may be the earliest indicator of ICANS among pediatric and young adult patients which may warrant closer monitoring, with more frequent CAPD assessments.

scholarly journals Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)

2022 ◽  
Vol 10 (1) ◽  
pp. e003847
Author(s):  
Marc Wehrli ◽  
Kathleen Gallagher ◽  
Yi-Bin Chen ◽  
Mark B Leick ◽  
Steven L McAfee ◽  
...  
Keyword(s):  
T Cell ◽  
Effector Cell ◽  
Standard Treatment ◽  
Treatment Guidelines ◽  
Immune Effector Cell ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T ◽  
Steroid Refractory

In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis. At our institution, anakinra has become the standard treatment for the management of steroid-refractory ICANS with or without CRS, based on recent animal data demonstrating the role of IL-1 in the pathogenesis of ICANS/CRS. Here, we retrospectively analyzed clinical and laboratory parameters, including serum cytokines, in 14 patients at our center treated with anakinra for steroid-refractory ICANS with or without CRS after standard treatment with tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) CD19-targeting CAR T. We observed statistically significant and rapid reductions in fever, inflammatory cytokines, and biomarkers associated with ICANS/CRS after anakinra treatment. With three daily subcutaneous doses, anakinra did not have a clear, clinically dramatic effect on neurotoxicity, and its use did not result in rapid tapering of corticosteroids; although neutropenia and thrombocytopenia were common at the time of anakinra dosing, there were no clear delays in hematopoietic recovery or infections that were directly attributable to anakinra. Anakinra may be useful adjunct to steroids and tocilizumab in the management of CRS and/or steroid-refractory ICANs resulting from CAR T-cell therapies, but prospective studies are needed to determine its efficacy in these settings.

scholarly journals Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR-T-cell treatment

2022 ◽  
Author(s):  
Raphael Teipel ◽  
Frank P Kroschinsky ◽  
Michael Kramer ◽  
Theresa Kretschmann ◽  
Katharina Egger-Heidrich ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Markers Of Inflammation ◽  
Car T Cell Therapy ◽  
Significant Difference ◽  
Car T ◽  
Before And After

Inflammation plays an important role in CAR-T-cell therapy, especially in the pathophysiology of cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Clonal hematopoiesis of indetermined potential (CHIP) has also been associated with chronic inflammation. The relevance of CHIP in the context of CAR-T-cell treatment is currently widely unknown. We longitudinally evaluated the prevalence of CHIP, using a targeted deep sequencing approach in a cohort of patients with r/r B-NHL before and after CAR-T-cell treatment. The aim was to define the prevalence and variation of CHIP over time and to assess the influence on clinical inflammation syndromes (CRS/ICANS), cytopenia and outcome. Overall, 32 patients were included. CHIP was found in 11 of 32 patients (34 %) before CAR-T-cell therapy. CHIP progression was commonly detected in the later course. Patients with CHIP showed a comparable response rate to CAR-T-cell treatment but had an improved OS (not reached vs. 265 days, p=0.003). No significant difference was observed in terms of the occurrence and severity of CRS/ICANS, therapeutic usage of tocilizumab and glucocorticosteroids, paraclinical markers of inflammation (except ferritin) or dynamics of hematopoietic recovery. CHIP is commonly observed in patients undergoing CD19-directed CAR-T-cell therapy and is not associated with an inferior outcome.

scholarly journals Pre-Infusion Neurofilament Light Chain (NfL) Levels Predict the Development of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) - a Multicenter Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2841-2841
Author(s):  
Omar H Butt ◽  
Alice Y. Zhou ◽  
Paolo F. Caimi ◽  
Paul-Robert Derenoncour ◽  
Kenneth Lee ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Post Infusion ◽  
History Of

Abstract Chimeric antigen receptor (CAR) T-cell therapy is often associated with neurological complications termed immune effector cell-associated neurotoxicity syndrome (ICANS). There remains a critical need to identify patients most at risk for ICANS. Yet a biomarker for the development of ICANS is lacking. This retrospective multicenter study evaluates pre-infusion levels of plasma neurofilament light chain (NfL), a marker of neurodegeneration, as a predictive biomarker the development of ICANS. Study inclusion criteria included available pre-infusion (up to 4 weeks prior to lymphodepletion) plasma from patients treated with a CAR T cell therapy (n = 30, 36% with ICANS, ASTCT consensus ICANS grade range 1-4). Exclusion criteria included confounding diagnoses known to elevate NfL levels (e.g. dementia, recent stroke). Plasma NfL was assayed using a Simoa HD-X kit (Quanterix TM). Demographic (age, sex), oncologic (primary, stage, mean tumor volume (MTV), and history of central nervous system (CNS) involvement), and medical history (history of non-oncologic CNS disease or neuropathy) were obtained from the medical record. MTV was derived from total lesion burden on pre-infusion positron emission tomography (PET) scans using a 41% maximum standard uptake value (SUV) threshold. Pre-infusion (i.e. during lymphodepletion) and Post-infusion Day 1 (D1) platelet count, C-reactive protein (CRP), fibrinogen, lactate dehydrogenase (LDH), and ferritin levels were also obtained from the medical record. Group comparisons used log-rank testing, followed by receiver operating characteristic (ROC) curve classification and hierarchical clustering. Validation testing used a 10,000 fold cross-validation on 80% of the data. Finally, demographic and clinical characteristics correlated with pre-infusion biomarkers using point-biserial and Spearman (rank) correlation. Our results demonstrated that individuals who would go on to develop ICANS had elevations in pre-infusion NfL ([87.6 v 29.4 pg/ml; Fig 1A], p = 0.00004) with excellent classification accuracy for the development of ICANS (AUC 0.96; Fig 1B), sensitivity (0.91) and specificity (0.95). NfL further correlated with ICANS development (r = 0.74, p < 0.0001; Fig 1C). Among known post-infusion risk factors, D1 ferritin had the highest classification accuracy, but was inferior to baseline NfL (p < 0.05; Fig 1B). Both baseline NfL and D1 ferritin elevations clustered with ICANS grade (Fig 1D). Our findings show that pre-infusion plasma NfL levels are a robust early marker for the development of ICANS that exceeds known post-infusion markers. This suggests the risk of developing ICANS reflects pre-existing latent neuroaxonal injury. Predictive identification of patients at risk of developing ICANS prior to cellular infusion would permit early, preemptive or prophylactic ICANS-directed therapies, thereby improving patient outcomes. Figure 1: Baseline (pre-infusion) NfL Levels in ICANS (A) Baseline (pre-infusion) levels of NfL in patients who develop Grade 0 ICANS, Grade 1-2 ICANS, and Grade 3+ ICANS. (B) Receiver operating characteristic curve classification of patients who developed any grade ICANS (1+) vs grade 0 for baseline NfL and post-infusion day 1 (D1) markers. (C) Correlation between pre-treatment factors and pre-infusion biomarkers. All significant relationships after correction for multiple comparisons using false discovery rate (FDR) are outlined (*). (D) Hierarchical clustering of age, baseline NfL, and D1 markers. Clusters associating with ICANS are labeled in red, while those associating with cytokine release syndrome (CRS) are in blue. Figure 1 Figure 1. Disclosures Caimi: Verastem: Consultancy; ADC Theraputics: Consultancy, Research Funding; Genentech: Research Funding; XaTek: Patents & Royalties: Royalties from patents (wife); Kite Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Amgen Therapeutics.: Consultancy; TG Therapeutics: Honoraria. de Lima: BMS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotec: Research Funding. Campian: AbbVie, Inc.: Speakers Bureau; NeoImmuneTech: Research Funding. Ghobadi: Amgen: Consultancy, Research Funding; Atara: Consultancy; Wugen: Consultancy; Celgene: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding.

scholarly journals Reactions Related to CAR-T Cell Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Lele Miao ◽  
Zhengchao Zhang ◽  
Zhijian Ren ◽  
Yumin Li
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Adverse Reactions ◽  
Tumor Lysis Syndrome ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Life Threatening

The application of chimeric antigen receptor (CAR) T-cell therapy as a tumor immunotherapy has received great interest in recent years. This therapeutic approach has been used to treat hematological malignancies solid tumors. However, it is associated with adverse reactions such as, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), off-target effects, anaphylaxis, infections associated with CAR-T-cell infusion (CTI), tumor lysis syndrome (TLS), B-cell dysplasia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) and coagulation disorders. These adverse reactions can be life-threatening, and thus they should be identified early and treated effectively. In this paper, we review the adverse reactions associated with CAR-T cells, the mechanisms driving such adverse reactions, and strategies to subvert them. This review will provide important reference data to guide clinical application of CAR-T cell therapy.

scholarly journals Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline

2021 ◽  
Author(s):  
Bianca D. Santomasso ◽  
Loretta J. Nastoupil ◽  
Sherry Adkins ◽  
Christina Lacchetti ◽  
Bryan J. Schneider ◽  
...  
Keyword(s):  
T Cell ◽  
Supportive Care ◽  
Effector Cell ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Immune Effector Cell ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy. METHODS A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021. RESULTS The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell–related toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell–associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell–associated neurotoxicity syndrome should be managed with corticosteroids and supportive care. Additional information is available at www.asco.org/supportive-care-guidelines .

Neurotoxicity—CAR T-cell therapy: what the neurologist needs to know

2020 ◽  
Vol 20 (4) ◽  
pp. 285-293 ◽  
Author(s):  
Lorna Neill ◽  
Jeremy Rees ◽  
Claire Roddie
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Cerebral Oedema ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Innovative Therapies ◽  
Infection Disease

Chimeric antigen receptor (CAR) T-cell therapy is one of the most innovative therapies for haematological malignancies to emerge in a generation. Clinical studies have shown that a single dose of CAR T-cells can deliver durable clinical remissions for some patients with B-cell cancers where conventional therapies have failed.A significant complication of CAR therapy is the immune effector cell-associated neurotoxicity syndrome (ICANS). This syndrome presents a continuum from mild tremor to cerebral oedema and in a minority of cases, death. Management of ICANS is mainly supportive, with a focus on seizure prevention and attenuation of the immune system, often using corticosteroids. Parallel investigation to exclude other central nervous system pathologies (infection, disease progression) is critical. In this review, we discuss current paradigms around CAR T-cell therapy, with a focus on appropriate investigation and management of ICANS.

scholarly journals How I treat adverse effects of CAR-T cell therapy

ESMO Open ◽  
2020 ◽  
Vol 4 (Suppl 4) ◽  
pp. e000746 ◽  
Author(s):  
Lucrecia Yáñez ◽  
Ana Alarcón ◽  
Miriam Sánchez-Escamilla ◽  
Miguel-Angel Perales
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Early Recognition ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigenreceptor (CAR) T cell therapy has demonstrated efficacy in B cell malignancies, particularly for acute lymphoblastic leukaemia (ALL) and non‑Hodgkin lymphomas. However, this regimen is not harmless and, in some patients, can lead to a multi organ failure. For this reason, the knowledge and the early recognition and management of the side effects related to CAR-T cell therapy for the staff is mandatory. In this review, we have summarised the current recommendations for the identification, gradation and management of the cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as infections, and related to CAR-T cell therapy.

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