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Nat Rev Immunol ; 22(2): 85-96, 2022 02.
Article in English | MEDLINE | ID: covidwho-2133458


A paradigm shift has recently occurred in the field of cancer therapeutics. Traditional anticancer agents, such as chemotherapy, radiotherapy and small-molecule drugs targeting specific signalling pathways, have been joined by cellular immunotherapies based on T cell engineering. The rapid adoption of novel, patient-specific cellular therapies builds on scientific developments in tumour immunology, genetic engineering and cell manufacturing, best illustrated by the curative potential of chimeric antigen receptor (CAR) T cell therapy targeting CD19-expressing malignancies. However, the clinical benefit observed in many patients may come at a cost. In up to one-third of patients, significant toxicities occur that are directly associated with the induction of powerful immune effector responses. The most frequently observed immune-mediated toxicities are cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. This Review discusses our current understanding of their pathophysiology and clinical features, as well as the development of novel therapeutics for their prevention and/or management.

Neoplasms , Neurotoxicity Syndromes , Antigens, CD19 , Cytokine Release Syndrome/etiology , Humans , Immunotherapy/adverse effects , Immunotherapy, Adoptive/adverse effects , Neoplasms/drug therapy , Neurotoxicity Syndromes/drug therapy , Neurotoxicity Syndromes/etiology , Receptors, Antigen, T-Cell/genetics
Nat Med ; 28(4): 735-742, 2022 04.
Article in English | MEDLINE | ID: covidwho-1895598


High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study ( NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62-90) and 89% ORR (95% CI, 75-97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.

Biological Products , Lymphoma, Large B-Cell, Diffuse , Antigens, CD19 , Biological Products/adverse effects , Cytokine Release Syndrome , Humans , Immunotherapy, Adoptive/adverse effects , Lymphoma, Large B-Cell, Diffuse/therapy , Neoplasm Recurrence, Local
Korean J Radiol ; 22(12): 1938-1945, 2021 12.
Article in English | MEDLINE | ID: covidwho-1497013


Breast radiologists are increasingly seeing patients with axillary adenopathy related to COVID-19 vaccination. Vaccination can cause levels I-III axillary as well as cervical lymphadenopathy. Appropriate management of vaccine-related adenopathy may vary depending on clinical context. In patients with current or past history of malignancy, vaccine-related adenopathy can be indistinguishable from nodal metastasis. This article presents imaging findings of oncology patients with adenopathy seen in the axilla or neck on cross-sectional imaging (breast MRI, CT, or PET-CT) after COVID-19 vaccination. Management approach and rationale is discussed, along with consideration on strategies to minimize false positives in vaccinated cancer patients. Time interval between vaccination and adenopathy seen on breast MRI, CT, or PET-CT is also reported.

Breast Neoplasms , COVID-19 , Lymphadenopathy , Vaccines , Axilla , Breast Neoplasms/diagnostic imaging , COVID-19 Vaccines , Female , Fluorodeoxyglucose F18 , Humans , Lymphadenopathy/diagnostic imaging , Magnetic Resonance Imaging , Positron Emission Tomography Computed Tomography , SARS-CoV-2