Journal for immunotherapy of cancer
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J Immunother Cancer · Nov 2019
Review Case Reports Meta AnalysisRadiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature.
Neurologic complications as myelitis are very rare but extremely deleterious adverse effects of both immunotherapy and radiotherapy. Many recent studies have focused on the possible synergy of these two treatment modalities due to their potential to enhance each other's immunomodulatory actions, with promising results and a safe tolerance profile. ⋯ The confinement within the radiation field and the latency of appearance are suggestive of delayed radiation myelopathy. Nevertheless, the relatively low dose of radiation received and the full recovery after pembrolizumab discontinuation and steroid therapy plead for the contribution of both radiotherapy and immunotherapy in the causality of this complication, as an enhanced inflammatory reaction on a focal post-radiation chronic inflammatory state. In the three previously described cases of myelopathy occurring after radiotherapy and immunotherapy, a complete recovery had not been obtained and the immunotherapy was not rechallenged. The occurrence of a radiation recall phenomenon, in this case, can not be excluded, and radiation recall myelitis has already been described with chemotherapy and targeted therapy. Safe rechallenges with the incriminated drug, even immunotherapy, have been reported after radiation recall, but we describe it for the first time after myelitis.
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J Immunother Cancer · Nov 2019
Case ReportsSevere early hepatitis B reactivation in a patient receiving anti-CD19 and anti-CD22 CAR T cells for the treatment of diffuse large B-cell lymphoma.
Hepatitis B virus (HBV) reactivation is commonly seen in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Little is known about the risk of HBV reactivation after chimeric antigen receptor T-cell (CAR T) immunotherapy for the treatment of refractory/relapsed malignant B-cell lymphoma. ⋯ Our study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL.
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J Immunother Cancer · Nov 2019
ReviewImmune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors.
Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15-60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. ⋯ Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.
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J Immunother Cancer · Nov 2019
Multicenter StudyCombined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study.
Uveal melanoma (UM) is highly refractory to treatment with dismal prognosis in advanced stages. The value of the combined checkpoint blockade with CTLA-4 and PD-1 inhibition in metastatic UM is currently unclear. ⋯ The tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.
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J Immunother Cancer · Nov 2019
Moving forward to address key unanswered questions on targeting PD-1/PD-L1 in cancer: limitations in preclinical models and the need to incorporate human modifying factors.
The tremendous clinical success of immune checkpoint inhibition (ICI), particularly targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1/2 (PD-L1/2) pathway, has resulted in application to multiple cancers, as a monotherapy and as a companion to both conventional and novel agents. Despite this, the precise mechanisms underlying the anti-tumor effects of PD-1/PD-L1 blockade remain unclear. Emphasis has centered on its reversal of tumor-specific CD8+ T-cell exhaustion, although many cell types and processes are likely impacted. ⋯ However, these mouse models often do not adequately reflect the tumor progression and cellular and genetic heterogeneity found within human cancers. Furthermore, laboratory mice also present with a vastly restricted immune profile compared to humans. This commentary discusses some of the critical questions that need to be addressed to optimize the use of ICI as well as caveats and limitations for consideration when extrapolating preclinical mouse data to the human cancer scenario.