Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition — A Descriptive Observational Retrospective Multicenter Analysis

Introduction Immune checkpoint inhibitors (ICI) are increasingly being used to treat numerous cancer types. Together with improved recognition of toxicities, this has led to more frequent identification of rare immune-related adverse events (irAE), for which specific treatment strategies are needed. Neutropenia is a rare hematological irAE that has a potential for a high mortality rate because of its associated risk of sepsis. Prompt recognition and timely treatment of this life-threatening irAE are therefore critical to the outcome of patients with immune-related neutropenia. Methods This multicenter international retrospective study was conducted at 17 melanoma centers to evaluate the clinical characteristics, diagnostics, treatment, and outcomes of melanoma patients with grade 4 neutropenia (<500 neutrophils/µl blood) treated with ICI between 2014 and 2020. Some of these patients received metamizole in addition to ICI (ICI+/met+). Bone marrow biopsies (BMB) of these patients were compared to BMB from non-ICI treated patients with metamizole-induced grade 4 neutropenia (ICI-/met+). Results In total, 10 patients (median age at neutropenia onset: 66 years; seven men) with neutropenia were identified, equating to an incidence of 0.14%. Median onset of neutropenia was 6.4 weeks after starting ICI (range 1.4–49.1 weeks). Six patients showed inflammatory symptoms, including fever (n=3), erysipelas (n=1), pharyngeal abscess (n=1), and mucositis (n=1). Neutropenia was diagnosed in all patients by a differential blood count and additionally performed procedures including BMB (n=5). Nine of 10 patients received granulocyte colony-stimulating factors (G-CSF) to treat their grade 4 neutropenia. Four patients received systemic steroids (including two in combination with G-CSF, and one in combination with G-CSF and additional ciclosporin A). Four patients were treated with one or more antibiotic treatment lines, two with antimycotic treatment, and one with additional antiviral therapy. Five patients received metamizole concomitantly with ICI. One fatal outcome was reported. BMB indicated a numerically lower CD4+ to CD8+ T cells ratio in patients with irNeutropenia than in those with metamizole-induced neutropenia. Conclusion Grade 4 neutropenia is a rare but potentially life-threatening side effect of ICI treatment. Most cases were sufficiently managed using G-CSF; however, adequate empiric antibiotic, antiviral, and antimycotic treatments should be administered if neutropenic infections are suspected. Immunosuppression using corticosteroids may be considered after other causes of neutropenia have been excluded

Prévalence des génotypes des papillomavirus humains chez des patients séropositifs pour le VIH (argumentaire pour une vaccination universelle anti-HPV)

L incidence des carcinomes anaux HPV-induits ne diminue pas chez les hommes VIH+ ayant des rapports sexuels avec les hommes (HSH) malgré l ère des trithérapies. L objectif de cette étude est de déterminer la prévalence des HPV chez des patients VIH dans un centre parisien et d en analyser les facteurs de risque. METHODELes hommes et femmes VIH+ du service de maladies infectieuses de l hôpital Tenon ayant eu un frottis à la recherche d HPV étaient inclus rétrospectivement. RESULTATS 93 HSH et 15 femmes âgés de 27 à 73 ans étaient analysés. Parmi les 33% des hommes qui avaient un examen clinique anormal, 70% de condylomes et 6,7% de dysplasies de bas grade étaient trouvés, alors que chez les femmes, les dysplasies de bas grade (60%) étaient plus fréquentes que les condylomes (30%).Les HPV 16 et 52 étaient majoritairement représentés avec des prévalences de 28% et 30% respectivement. Un portage asymptomatique était retrouvé chez 71,6% des patients avec une prévalence de 60% des HPV à haut risque (HR) et de 60,1% d'infection par plus d'un HPV. Cette étude n'a pas mis en évidence de facteur de risque d'infection par HPV. DISCUSSIONIl existe une forte prévalence d infection anale par HPV chez les HSH VIH+. La vaccination anti-HPV des patients HSH a montré son efficacité dans d'autres pays. Parallèlement, un dépistage précoce des néoplasies intraépithéliales anales et leur traitement permettraient de diminuer l incidence des carcinomes invasifs. CONCLUSION Les maladies HPV induites sont un enjeu de santé publique avec plus de 5% des cancers dans le monde attribuables aux HPV à HR. La vaccination, actuellement débattue, pourrait prévenir ce risque chez les HSHPARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF

Yield of FDG PET/CT for Defining the Extent of Disease in Patients with Kaposi Sarcoma

International audienceBackground: Positron emission tomography/computed tomography with fluorodeoxyglucose (F-18) (FDG PET/CT) is increasingly used in Kaposi sarcoma (KS), but its value has not been assessed. Objectives: In this study, we aimed to evaluate the diagnostic accuracy of FDG PET/CT to define the extent of disease in KS. Methods: Consecutive patients with KS referred to our department for FDG PET/CT were included. The diagnostic accuracy of FDG PET/CT for cutaneous and extra-cutaneous KS staging was assessed on a per lesion basis compared to staging obtained from clinical examination, standard imaging, endoscopy, histological analyses, and follow-up. Results: From 2007 to 2017, 75 patients with FDG PET/CT were analyzed. The sensitivity and specificity of FDG PET/CT for the overall detection of KS lesions were 71 and 98%, respectively. Sensitivity and specificity were 100 and 85% for lymph nodes, 87 and 98% for bone, 87 and 100% for lungs, and 100 and 100% for muscle involvement, whereas sensitivity was only 17% to detect KS digestive involvement. The sensitivity of the diagnostic for KS cutaneous involvement increased from 73 to 88% when using a whole-body examination. Conclusion: FDG PET/CT showed good sensitivity and specificity for KS staging (digestive involvement excepted) and could be used for staging patients with active KS

18FDG PET Assessment of Therapeutic Response in Patients with Advanced or Metastatic Melanoma Treated with First-Line Immune Checkpoint Inhibitors

International audienceBackground: Immune checkpoint inhibitors (ICI) are currently the first-line treatment for patients with metastatic melanoma. We investigated the value of positron emission tomography (PET) response criteria to assess the therapeutic response to first-line ICI in this clinical context and explore the potential contribution of total tumor metabolic volume (TMTV) analysis. Methods: We conducted a retrospective study in patients treated with first-line ICI for advanced or metastatic melanoma, with 18F-FDG PET/CT performed at baseline and 3 months after starting treatment. Patients’ metabolic response was classified according to PERCIST5 and imPERCIST 5 criteria. TMTV was recorded for each examination. Results: Twenty-nine patients were included. The median overall survival (OS) was 51.2 months (IQR 13.6—not reached), and the OS rate at 2 years was 58.6%. Patients classified as responders (complete and partial response) had a 90.9% 2-year OS rate versus 38.9% for non-responders (stable disease and progressive disease) (p = 0.03), for PERCIST5 and imPERCIST 5 criteria. The median change in metabolic volume was 9.8% (IQR −59–+140%). No significant correlation between OS and changes in TMTV was found. Conclusion: The evaluation of response to immunotherapy using metabolic imaging with PERCIST5 and imPERCIST5 was significantly associated with OS in patients with advanced or metastatic melanoma

Translating Molecules into Imaging—The Development of New PET Tracers for Patients with Melanoma

International audienceMelanoma is a deadly disease that often exhibits relentless progression and can have both early and late metastases. Recent advances in immunotherapy and targeted therapy have dramatically increased patient survival for patients with melanoma. Similar advances in molecular targeted PET imaging can identify molecular pathways that promote disease progression and therefore offer physiological information. Thus, they can be used to assess prognosis, tumor heterogeneity, and identify instances of treatment failure. Numerous agents tested preclinically and clinically demonstrate promising results with high tumor-to-background ratios in both primary and metastatic melanoma tumors. Here, we detail the development and testing of multiple molecular targeted PET-imaging agents, including agents for general oncological imaging and those specifically for PET imaging of melanoma. Of the numerous radiopharmaceuticals evaluated for this purpose, several have made it to clinical trials and showed promising results. Ultimately, these agents may become the standard of care for melanoma imaging if they are able to demonstrate micrometastatic disease and thus provide more accurate information for staging. Furthermore, these agents provide a more accurate way to monitor response to therapy. Patients will be able to receive treatment based on tumor uptake characteristics and may be able to be treated earlier for lesions that with traditional imaging would be subclinical, overall leading to improved outcomes for patients

Long-Term Outcome of Neoadjuvant Tyrosine Kinase Inhibitors Followed by Complete Surgery in Locally Advanced Dermatofibrosarcoma Protuberans

In locally advanced dermatofibrosarcoma protuberans (DFSP), imatinib mesylate has been described as an efficient neoadjuvant therapy. This retrospective study included patients with locally advanced DFSP who received neoadjuvant TKI (imatinib or pazopanib) from 2007 to 2017 at Saint Louis Hospital, Paris. The primary endpoint was the evaluation of the long-term status. A total of 27 patients were included, of whom nine had fibrosarcomatous transformation. The median duration of treatment was 7 months. The best response to TKI treatment before surgery, evaluated according to RECIST1.1 on MRI, consisted of complete/partial response (38.5%) or stability (46.2%). DFSP was surgically removed in 24 (89%) patients. A total of 23 patients (85%) were disease-free after 64.8 months of median follow-up (95% confidence interval 47.8; 109.3). One patient developed distant metastases 37 months after surgical tumor resection and finally died. Two patients (7%) did not get surgery because of metastatic progression during TKI treatment, and one patient refused surgery even though the tumor decreased by 30%. Treatment-related adverse events (AE) occurred in 23 patients (85%). Only four patients (imatinib: n = 3, pazopanib: n = 1) had grade ≥3 AE requiring temporary treatment disruption. Neoadjuvant TKI followed by complete surgery with micrographic analysis is an effective strategy for locally advanced and unresectable DFSP, with durable local recurrence disease-free survival

Increased risk of brain metastases among patients with melanoma and PROM2 expression in metastatic lymph nodes

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