Effectiveness of rituximab in treating immune-checkpoint-inhibitor-induced immune-related adverse events: results of a systematic review

Deftereos, Spyros; Georgonikou, D

doi:10.1016/j.annonc.2020.12.001

Cited by 12 publications

(7 citation statements)

References 5 publications

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“…A recent study found that aged anti-PD-1-treated mice developed TLS-like aggregates in irAE-affected tissue in a CXCL13-dependent fashion and that B cell depletion could attenuate ICI-inflicted toxicity [48]. So far, the use of rituximab for irAE management is limited to case reports [49]. These data together with our work reinforce B cells as a potential target for irAE treatment.…”

Section: Discussionsupporting

confidence: 74%

Toxicity-specific peripheral blood T and B cell dynamics in anti-PD-1 and combined immune checkpoint inhibition

Eijs

Verheijden

Wees

et al. 2023

Preprint

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Background Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of advanced malignancies, but come with a diverse spectrum of immune-related adverse events (irAEs). Studies into irAE mechanisms are needed to make a transition from expert-opinion to evidence-based irAE treatment strategies. Methods We aimed to longitudinally characterize peripheral blood T and B cell dynamics in ICI-treated patients developing irAEs and remaining irAE-free. PBMCs were immunophenotyped and functionally assessed with multicolor flow cytometry at baseline, after ±3 weeks and ±6 weeks or upon clinically relevant irAEs. Additionally, serum cytokine concentrations for 23 analytes were measured by multiplex immunoassay at the same timepoints. Results We analyzed samples from 44 ICI-treated patients (24 anti-PD-1 monotherapy, 20 combined anti-PD-1 and anti-CTLA-4; cICI), of whom 22 developed clinically relevant irAEs, and 10 healthy donors. IrAEs after cICI were characterized by significantly enhanced proliferation of Th1-associated, mainly effector memory T cells, as well as Th17-associated and possibly antibody-mediated immune responses. The latter response was reflected in cICI toxicity by rising CXCL13 and IL-21 levels, but without changes in CD21lo, memory, class-switched or newly activated B cell subsets. Anti-PD-1 monotherapy-inflicted irAEs were associated with a modestly enhanced Th1-associated response compared to irAE-free patients, only reflected by increasing serum CXCL9 and CXCL10, but without cellular changes in Th1/Tc1 subsets. PD-1+LAG-3+double-positive (DP) CD8+T cells retained their proinflammatory potential in all treatment groups, regardless of irAE development. Especially DP CD8+T cells showed enhanced cytotoxic capacity in patients with irAEs after cICI. In all patients with irAEs, highly cytotoxic CD57+CD8+T cells were abundant. Conclusions Peripheral blood immune responses are substantially different between cICI and anti-PD-1 monotherapy-treated patients. ICI-induced toxicity is clearly dominated by an enhanced Th1-associated response, but in cICI we also found evidence for Th17-associated and possibly antibody-mediated responses. CD4+effector memory T cells were the principal cycling cells in irAEs after cICI. Together, our data add to the growing body of evidence that irAEs may be antibody-mediated and driven by newly activated CD4+helper T cells, specifically after cICI.

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Section: Discussionsupporting

confidence: 74%

Toxicity-specific peripheral blood T and B cell dynamics in anti-PD-1 and combined immune checkpoint inhibition

Eijs

Verheijden

Wees

et al. 2023

Preprint

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“…In the case of peripheral nervous irAEs, after plasmapheresis and intravenous immunoglobulin in steroid-resistant cases, the most common third-line treatments are tocilizumab, infliximab, rituximab, mycophenolate, methotrexate, and cyclophosphamide ( June et al, 2017 ; Memarnejadian et al, 2017 ; Spain et al, 2017 ). Among these medications, rituximab has shown more effectiveness for MG, and other antibody-mediated NirAEs, due to the depletion of B lymphocytes ( Deftereos and Georgonikou 2021 ).…”

Section: Treatment and Management Recommendationsmentioning

confidence: 99%

Neurologic Toxicity of Immune Checkpoint Inhibitors: A Review of Literature

et al. 2022

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Immune checkpoint inhibitors have entailed a change of paradigm in the management of multiple malignant diseases and are acquiring a key role in an increasing number of clinical sceneries. However, since their mechanism of action is not limited to the tumor microenvironment, their systemic activity may lead to a wide spectrum of immune-related side effects. Although neurological adverse events are much less frequent than gastrointestinal, hepatic, or lung toxicity, with an incidence of <5%, their potential severity and consequent interruptions to cancer treatment make them of particular importance. Despite them mainly implying peripheral neuropathies, immunotherapy has also been associated with an increased risk of encephalitis and paraneoplastic disorders affecting the central nervous system, often appearing in a clinical context where the appropriate diagnosis and early management of neuropsychiatric symptoms can be challenging. Although the pathogenesis of these complications is not fully understood yet, the blockade of tumoral inhibitory signals, and therefore the elicitation of cytotoxic T-cell-mediated response, seems to play a decisive role. The aim of this review was to summarize the current knowledge about the pathogenic mechanisms, clinical manifestations, and therapeutic recommendations regarding the main forms of neurotoxicity related to checkpoint inhibitors.

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“… 87 With regard to rituximab, a systematic literature review identified no published cases of rituximab treated patients with ICI arthritis but did note that the drug was effective in 6/9 patients with neurologic irAE. 88 …”

Section: Ici-arthritis Managementmentioning

confidence: 99%

Monitoring and Management of the Patient with Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis: Current Perspectives

Chan¹,

Bass²

2022

JIR

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In this review, we draw from observational studies, treatment guidelines and our own clinical experience to describe approaches to monitoring and management of immune checkpoint inhibitor (ICI)-induced inflammatory arthritis, including polymyalgia rheumatica. This condition occurs in about 4% of ICI-treated cancer patients and can persist for a year or longer. Mild arthritis can generally be managed with non-steroidal anti-inflammatory drugs, intraarticular steroids injections and/or low dose corticosteroids. Higher grade arthritis should be brought under control with corticosteroids, but early introduction of a steroid-sparing agent is recommended to minimize steroid toxicity. In order to assess the effectiveness of any arthritis treatment, tender and swollen joint counts and patient reported measures of physical function, such as the health assessment questionnaire, should be obtained at each visit. Referral to a rheumatologist is recommended for patients with high grade arthritis to help guide the use of disease-modifying antirheumatic drugs.

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Effectiveness of rituximab in treating immune-checkpoint-inhibitor-induced immune-related adverse events: results of a systematic review

Cited by 12 publications

References 5 publications

Toxicity-specific peripheral blood T and B cell dynamics in anti-PD-1 and combined immune checkpoint inhibition

Toxicity-specific peripheral blood T and B cell dynamics in anti-PD-1 and combined immune checkpoint inhibition

Neurologic Toxicity of Immune Checkpoint Inhibitors: A Review of Literature

Monitoring and Management of the Patient with Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis: Current Perspectives

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