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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: Most patients with advanced-stage indolent non-Hodgkin lymphoma have multiple relapses. We assessed axicabtagene ciloleucel autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory indolent non-Hodgkin lymphoma.Methods: ZUMA-5 is a single-arm, multicentre, phase 2 trial being conducted at 15 medical cancer centres in the USA and two medical cancer centres in France. Patients were eligible if they were aged 18 years or older, with histologically confirmed indolent non-Hodgkin lymphoma (follicular lymphoma or marginal zone lymphoma), had relapsed or refractory disease, previously had two or more lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients underwent leukapheresis and received conditioning chemotherapy (cyclophosphamide at 500 mg/m2 per day and fludarabine at 30 mg/m2 per day on days -5, -4, and -3) followed by a single infusion of axicabtagene ciloleucel (2 × 106 CAR T cells per kg) on day 0. The primary endpoint was overall response rate (complete response and partial response) assessed by an independent review committee per Lugano classification. The primary activity analysis was done after at least 80 treated patients with follicular lymphoma had been followed up for at least 12 months after the first response assessment at week 4 after infusion. The primary analyses were done in the per-protocol population (ie, eligible patients with follicular lymphoma who had 12 months of follow-up after the first response assessment and eligible patients with marginal zone lymphoma who had at least 4 weeks of follow-up after infusion of axicabtagene ciloleucel). Safety analyses were done in patients who received an infusion of axicabtagene ciloleucel. This study is registered with ClinicalTrials.gov, NCT03105336, and is closed to accrual.Findings: Between June 20, 2017, and July 16, 2020, 153 patients were enrolled and underwent leukapheresis, and axicabtagene ciloleucel was successfully manufactured for all enrolled patients. As of data cutoff (Sept 14, 2020), 148 patients had received an infusion of axicabtagene ciloleucel (124 [84%] who had follicular lymphoma and 24 [16%] who had marginal zone lymphoma). The median follow-up for the primary analysis was 17·5 months (IQR 14·1-22·6). Among patients who were eligible for the primary analysis (n=104, of whom 84 had follicular lymphoma and 20 had marginal zone lymphoma), 96 (92%; 95% CI 85-97) had an overall response and 77 (74%) had a complete response. The most common grade 3 or worse adverse events were cytopenias (104 [70%] of 148 patients) and infections (26 [18%]). Grade 3 or worse cytokine release syndrome occurred in ten (7%) patients and grade 3 or 4 neurological events occurred in 28 (19%) patients. Serious adverse events (any grade) occurred in 74 (50%) patients. Deaths due to adverse events occurred in four (3%) patients, one of which was deemed to be treatment-related (multisystem organ failure).Interpretation: Axicabtagene ciloleucel showed high rates of durable responses and had a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma.Funding: Kite, a Gilead Company. [ABSTRACT FROM AUTHOR]

• No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. • By neutralizing a key inflammatory factor in the cytokine release syndrome in COVID-19, tocilizumab (TCZ) can block the cytokine storm and reduce the severity of the disease. • Our case-control study found that patients treated with TCZ had a lower index of mortality and/or invasive mechanical ventilation (IMV) requirement than patients without TCZ. • This result strongly suggests that TCZ may reduce the number of IMV requirements and/or mortality in patients with severe SARS-CoV-2 pneumonia. • This idea needs to be confirmed and spread in the medical community. No therapy has proven to be effective yet to reduce mortality and/or invasive mechanical ventilation (IMV) requirement in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment. We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: mortality and/or IMV requirement. Thirty patients were treated with TCZ and 176 patients were treated without TCZ. TCZ was used in patients in critical condition (oxygen therapy flow at TCZ onset was 10.5 L/min and 14/30 patients had ≥ 50% lung involvement on CT scan) as a rescue treatment (8/30 patients who died were not admitted in USC in regard to their comorbidities). However, mortality and/or IMV requirement were lower in patients with TCZ than in patients without TCZ (27% vs 52%, p = 0.009). Despite the small sample size in the TCZ group, this result suggests that TCZ reduces mortality and/or IMV requirement in patients with severe SARS-CoV-2 pneumonia. This notion needs to be confirmed and spread in the medical community. [ABSTRACT FROM AUTHOR]

• No drugs have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. • By neutralizing a key inflammatory factor in the cytokine release syndrome in COVID-19, tocilizumab (TCZ) can block the cytokine storm and reduce disease severity. • Our case-control study found that even though patients treated with TCZ had more comorbidities and presented with more severe forms, death and/or ICU admissions were higher in patients without TCZ. • This result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia. No therapy has yet proven effective in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment. We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: death and/or ICU admissions. Patients with TCZ (n = 20) had a higher Charlson comorbidity index (5.3 [±2.4] vs 3.4 [±2.6], P = 0.014), presented with more severe forms (higher level of oxygen therapy at 13 L/min vs 6 L/min, P < 0.001), and had poorer biological findings (severe lymphopenia: 676/mm3 vs 914/mm3, P = 0.037 and higher CRP level: 158 mg/L vs 105 mg/L, P = 0.017) than patients without TCZ (n = 25). However, death and/or ICU admissions were higher in patients without TCZ than in the TCZ group (72% vs 25%, P = 0.002). Despite the small sample size and retrospective nature of the work, this result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia. [ABSTRACT FROM AUTHOR]

Around the tenth day after diagnosis,∼20% of patients with coronavirus disease 2019 (COVID-19)−associated pneumonia evolve to-ward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a “cytokine storm.” Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19−associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg·d−1for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P<0.01), with no deaths, significant decreases in oxygen requirements (P<0.05), and more days without invasive mechanical ventilation (P<0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyper inflammatory respiratory failure in COVID-19 patients. [ABSTRACT FROM AUTHOR]