Unerwünschte Wirkungen der Immuntherapie

Widmann, Gerlig; Nguyen, Van Anh; Plaickner, J.; Jaschke, Werner

doi:10.1007/s00117-017-0285-0

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…The most common irAEs are dermatologic, including vitiligo, rash, and erythema. irAEs detectable in radiological examinations are colitis, pneumonitis, thyroiditis, hepatitis, pancreatitis, hypophysitis, and arthritis [ 23 , 24 ].…”

Section: Imaging Of Immune-related Adverse Eventsmentioning

confidence: 99%

“…Imaging findings are an organomegaly, reduced density of the pancreas, and increased density of the peripancreatic fat. In 18 F-FDG-PET/CT an increased FDG uptake had been described [ 23 ].…”

Section: Imaging Of Immune-related Adverse Eventsmentioning

confidence: 99%

“…Whereas colitis is more common with ipililumab therapy, pneumonitis is more commonly seen with PD-1 inhibitors nivolumab and pembrolizumab [ 23 ]. According to a meta-analysis including 3232 patients treated with PD-1 inhibitors and 1806 patients with PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab), it seems that PD-1 inhibitors have a higher incidence of pneumonitis compared with PD-L1 inhibitors [ 27 ].…”

Section: Imaging Of Immune-related Adverse Eventsmentioning

confidence: 99%

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Pitfalls in the radiological response assessment of immunotherapy

Beer

Hochmair

Prosch

2018

memo

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SummaryImmunotherapies comprise of a class of cancer therapies that are increasingly used for treatment of several cancer entities. Active immunotherapies encompassing immune checkpoint inhibitors are the most widespread class of immunotherapies, with indications for melanoma, non-small lung cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, and Hodgkin’s lymphoma. Immune checkpoint inhibitors have demonstrated unique response patterns that are not adequately captured by traditional response criteria such das the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization criteria. Consequently, adaptions of these criteria have been released such as the immune-related RECIST and immune RECIST, which account for the specialities of immunotherapies. Immunotherapies can cause a distinct set of adverse events such as pneumonitis, colitis, and hypophysitis. In addition, atypical treatment response patterns termed pseudoprogression have been observed. Thereby, new or enlarging lesions appear after treatment start and mimic tumor progression, which is followed by an eventual decrease in total tumor burden. In this review article we will describe pitfalls in the radiological response assessment of immunotherapies, focusing on pseudoprogression and imaging appearances of common immune-related adverse events.

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Section: Imaging Of Immune-related Adverse Eventsmentioning

confidence: 99%

Section: Imaging Of Immune-related Adverse Eventsmentioning

confidence: 99%

Section: Imaging Of Immune-related Adverse Eventsmentioning

confidence: 99%

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Pitfalls in the radiological response assessment of immunotherapy

Beer

Hochmair

Prosch

2018

memo

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“…Combination of ipilimumab with nivolumab is associated with a high rate (55%) of grade 3/4 adverse events leading to discontinuation in a third of those treated. Symptoms from ICIs may present as serious and life-threatening events, which require timely patient management and adequate therapeutic decisions [42][43][44][45][46][47]. The Oncology Nursing Society has an immunotherapy wallet card available for patients and providers, which warns that patients have a life-time risk of irAEs [40].…”

Section: In the Face Of Widespread Autoimmune Toxicities Insisting Tmentioning

confidence: 99%

Exploiting Autoimmunity Unleashed by an Off-Label Low-Dose Immune Checkpoint Blockade to Treat Advanced Cancer

Bakács¹,

Moss²,

Szász³

et al. 2018

Preprint

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As a result of the cancer immunotherapy revolution hundreds of clinical trials of the newly approved immunotherapies are now under way to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by blockade of co-inhibitory signals. While success stories of terminal cancer patients achieving complete remissions are accumulating, not enough research has been done into the risks of the new therapies. Since the use of immunotherapy is becoming more common, and is expected to develop into first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the nemesis of immunotherapy. Immune-related adverse events (IrAEs) could affect any tissue, their incidence may reach up to 90% of patients and toxicity is dose-dependent. While the combination of two immune checkpoint inhibitors (ICIs) increased efficacy, the incidence of severe adverse events was also increased. Apparently, ICIs cannot be restricted to the targeted anti-tumor T cell population. The long lasting objective of cancer regression can only be achieved by paying a price: tolerance to healthy self tissues is compromised. In the face of an ipilimumab induced pan-lymphocytic activation, a therapeutic paradigm shift is required. The task is not desperately trying to put the genie back in the bottle by immune suppressive treatments, but instead harnessing the autoimmune forces by an off label low-dose combined anti-CTLA-4 and anti-PD1 antibody blockade, which is supplemented with conventional interleukin-2 stimulation and hyperthermia. The proof-of-principle of the low-dose-combination therapy was demonstrated in a heavily pre-treated triple negative breast cancer (TNBC) patient with far advanced pulmonary metastases and severe shortness of breath, who had exhausted all conventional treatment. Her pulmonary metastases went into complete remission with transient WHO I-II diarrhea and skin rash. She lived for 27 months after starting the low-dose-combination therapy. She had recurrence as a sternal mass and pleural metastases up to 3 cm. Since the low-dose-combination protocol consists only of approved drugs and treatments, this exceptional response should instigate further research efforts.

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“…4,[9][10][11][12][13] Molecular imaging, especially positron emission tomography using antibodies conjugated with radionuclides (immuno-PET), allows for accurate and noninvasive evaluation of target levels. [14][15][16] Due to the high sensitivity and resolution, immuno-PET has been successfully applied to interrogate the relationship between tissue uptake and clinical responses toward antibody treatment. [17][18][19] Thus, immuno-PET could be a crucial tool to test the biomarker hypothesis of immune checkpoint proteins for immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Immuno-PET Tracer to Image PD-L1

et al. 2019

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The rapid ascension of immune checkpoint blockade treatments has placed an emphasis on the need for viable, robust, and noninvasive imaging methods for immune checkpoint proteins, which could be of diagnostic value. Immunoconjugate-based positron emission tomography (immuno-PET) allows for sensitive and quantitative imaging of target levels and has promising potential for the noninvasive evaluation of immune checkpoint proteins. However, the advancement of immuno-PET is currently limited by available imaging tools, which heavily rely on full-length IgGs with Fc-mediated effects and are heterogeneous mixtures upon random conjugation with chelators for imaging. Herein, we have developed a site-specific αPD-L1 Fab conjugate with the chelator 1,4,7triazacyclononane-N,N′,N″-triacetic acid (NOTA), enabling radiolabeling for PET imaging, using the amber suppression-mediated genetic incorporation of unnatural amino acid (UAA), pazidophenylalanine. This Fab conjugate is homogeneous and demonstrated tight binding toward the PD-L1 antigen in vitro. The radiolabeled version, 64 Cu-NOTA-αPD-L1, has been employed in PET imaging to allow for effective visualization and mapping of the biodistribution of PD-L1 in two normal mouse models, including the capturing of different PD-L1 expression levels in the spleens of the different mouse types. Follow-up in vivo blocking studies and ex vivo fluorescent staining further validated specific tissue uptakes of the imaging agent. This approach illustrates the utility of UAA-based site-specific Fab conjugation as a general strategy for making sensitive PET imaging probes, which could facilitate the elucidation of the roles of a wide variety of immune checkpoint proteins in immunotherapy.

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Unerwünschte Wirkungen der Immuntherapie

Cited by 6 publications

References 32 publications

Pitfalls in the radiological response assessment of immunotherapy

Pitfalls in the radiological response assessment of immunotherapy

Exploiting Autoimmunity Unleashed by an Off-Label Low-Dose Immune Checkpoint Blockade to Treat Advanced Cancer

Site-Specific Immuno-PET Tracer to Image PD-L1

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