Hyperprogressive disease: A distinct pattern of progression to immune checkpoint inhibitors

2020 ◽  
Author(s):  
Maria I. Toki ◽  
Nikos Syrigos ◽  
Kostas Syrigos
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Distinct Pattern ◽  
Hyperprogressive Disease

Immune checkpoint inhibitor–associated hypercalcaemia

2020 ◽  
Author(s):  
Hassan Izzedine ◽  
Thibaud Chazal ◽  
Rimda Wanchoo ◽  
Kenar D Jhaveri
Keyword(s):  
Immune System ◽  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Endocrine Disease ◽  
Oncological Patients ◽  
Hyperprogressive Disease

Abstract Immune checkpoint inhibitors (CPIs) have recently become a cornerstone for the treatment of different advanced cancers. These drugs have the ability to reactivate the immune system against tumour cells but can also trigger a myriad of side effects, termed immune-related adverse events (irAEs). Although there are numerous reports of CPI-related endocrinopathies, hypercalcaemia as a suspected irAE is not well documented. The mechanisms of CPI hypercalcaemia are not clearly established. However, in our review, four distinct causes emerged: endocrine disease-related, sarcoid-like granuloma, humoral hypercalcaemia due to parathyroid-related hormone and hyperprogressive disease following CPI initiation. Prompt recognition of hypercalcaemia and the institution of therapy can be lifesaving, affording the opportunity to address the underlying aetiology. In this review we discuss the incidence, diagnosis and management of immune-related hypercalcaemia in oncological patients receiving CPI agents.

scholarly journals Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors

2019 ◽  
Vol 30 ◽  
pp. xi25
Author(s):  
P. Ayala de Miguel ◽  
J. López Gallego ◽  
I. Gorospe García ◽  
A. Illán Varella ◽  
P.R. Rivera Vargas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hyperprogressive Disease

Hyperprogressive disease in patients with recurrent high grade gliomas treated with immune checkpoint inhibitors or other therapies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13575-e13575
Author(s):  
Laura Donovan ◽  
Samuel Gedailovich ◽  
Adela Joanta-Gomez ◽  
Jessica Schulte ◽  
Teri Nguyen Kreisl ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Fold Increase ◽  
Tumor Growth Rate ◽  
Control Group ◽  
High Grade ◽  
Advanced Cancer Patients ◽  
High Grade Gliomas ◽  
Hyperprogressive Disease

e13575 Background: Hyperprogressive disease (HPD) has been described in solid tumor patients treated with immune checkpoint inhibitors (ICI). HPD is defined as a ≥2-fold increase in tumor growth rate (TGR) following initiation of ICI. HPD has not been explored in patients with high grade gliomas (HGG) on ICI or standard cytotoxic regimens. In advanced cancer patients receiving ICI, MDM2/4 amplification or EGFR alterations, both found in HGG, correlated with HPD. We compared the rate of HPD in recurrent HGG patients receiving ICIs to those treated with non-immunotherapy agents. Methods: Patients with HGG on ICIs for 1st or 2nd recurrence were compared to a control group receiving other therapies at 1st recurrence. Patients with prior or concurrent bevacizumab or anti-VEGFR were excluded due to pseudoresponse and decreased enhancement with these drugs. HPD was calculated by comparing TGR immediately before and after treatment. Results: 49 patients met inclusion criteria (27 ICI, 25 control). 25/27 patients treated with ICIs and 20/22 patients in the control group had complete imaging and were eligible for analysis. In the ICI group, 60% were men (15/25) and 88% (22/25) had a diagnosis of GBM. 68% were treated at first progression (17/25). Controls were 80% male (16/20) and all had a diagnosis of GBM. 30% (6/20) were 65 years or older at diagnosis in the control group compared to 28% (7/25) in the ICI group. In total, 7/25 patients met criteria for HPD in the ICI group (28%) compared to 4/20 patients in the control group (20%). 10/25 patients (5/7 with HPD) in the ICI group and 8/20 patients (2/4 with HPD) in the control group had next generation sequencing of their tumors. EGFR alterations and MDM2/4 amplifications were not associated with HPD whereas PTEN mutations were more common in the HPD group (71% HPD vs. 33.3% no HPD). Conclusions: HPD is observed in patients with HGG treated with ICI at comparable rates to those with other cancers, but was also observed in 20% of patients receiving other therapies. While the numbers are small, PTEN mutations may be associated with HPD in patients with HGG. In contrast to other solid tumors, EGFR alterations and MDM2/4 amplifications were not associated with HPD in HGG.

scholarly journals Hyperprogressive Disease in Cancers Treated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Pan Shen ◽  
Liang Han ◽  
Xin Ba ◽  
Kai Qin ◽  
Shenghao Tu
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Retrospective Studies ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Predictive Biomarkers ◽  
Rapid Progression ◽  
Hyperprogressive Disease

Immunotherapy, which takes advantage of the immune system to eliminate cancer cells, has been widely studied and applied in oncology. Immune checkpoint inhibitors (ICIs) prevent the immune system from being turned off before cancer cells are eliminated. They have proven to be among the most promising and effective immunotherapies, with significant survival benefits and durable responses in diverse tumor types. However, an increasing number of retrospective studies have found that some patients treated with ICIs experience unusual responses, including accelerated proliferation of tumor cells and rapid progression of the disease, with poor outcomes. Such unexpected adverse events are termed hyperprogressive disease (HPD), and their occurrence suggests that ICIs are detrimental to a subset of cancer patients. HPD is common, with an incidence ranging between 4 and 29% in several cancer types. However, the mechanisms of HPD remain poorly understood, and no clinical predictive factors of HPD have been identified. In this review, we summarize current findings, including retrospective studies and case reports, and focus on several key issues including the defining characteristics, predictive biomarkers, potential mechanisms of HPD, and strategies for avoiding HPD after ICI treatment.

scholarly journals Evaluation of Response to Immune Checkpoint Inhibitors Using a Radiomics, Lesion-Level Approach

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6050
Author(s):  
Chorog Song ◽  
Hyunjin Park ◽  
Ho Yun Lee ◽  
Seunghak Lee ◽  
Joong Hyun Ahn ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Ct Scans ◽  
Advanced Lung Cancer ◽  
Rank Test ◽  
Multivariable Logistic Regression Analysis ◽  
Log Rank Test ◽  
Lesion Level ◽  
Hyperprogressive Disease

Conventional methods to determine the response to immune checkpoint inhibitors (ICIs) are limited by the unique responses to an ICI. We performed a radiomics approach for all measurable lesions to identify radiomic variables that could distinguish hyperprogressive disease (HPD) on baseline CT scans and classify a dissociated response (DR). One hundred and ninety-six patients with advanced lung cancer, treated with ICI monotherapy, who underwent at least three CT scans, were retrospectively enrolled. For all 621 measurable lesions, HPDv was determined from baseline CT scans using the tumor growth kinetics (TGK) ratio, and radiomics features were extracted. Multivariable logistic regression analysis of radiomics features was performed to discriminate DR. Radiomics features that significantly discriminated HPDv on baseline CT differed according to organ. Of the 196 patients, 54 (27.6%) had a DR and 142 (72.4%) did not have a DR. Overall survival in the group with a DR was significantly inferior to that in the group without a DR (log rank test, p = 0.04). Our study shows that lesion-level analysis using radiomics features has great potential for discriminating HPDv and understanding heterogeneous tumor progression, including a DR, after ICI treatment.

scholarly journals What’s the difference between hyperprogressive disease and progressive disease for patients with treated immune checkpoint inhibitors?

2021 ◽  
Author(s):  
Hasan Çağrı Yıldırım ◽  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Hakan Taban ◽  
Feride Yilmaz ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Ecog Performance Status ◽  
The Difference ◽  
Hyperprogressive Disease ◽  
The Relationship

Abstract Background Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. Some of the patients in this group, which is considered to have hyperprogressive disease (HPD), have a shorter overall survival compared to progressive disease (PD). Therefore, biomarkers are needed to differentiate between HPD and PD. Here, we evaluated PILE score to differentiate HPD from PD in patients treated with ICI. Methods Ninety-five patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any type of cancer with progression according to RECIST criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system was calculated, including PIV (< median vs. ≥ median), LDH (normal and > normal), and ECOG performance status (0 vs. ≥ 1). The relationship between PILE score and HPD was examined. Results The median follow-up was 6.6 months and the median OS of all cohort were 11.18 ± 1.36 months. The patients in the HPD group had decreased OS (4.77 ± 0.89 vs. 13.94 ± 1.80 months, p <0.001) and PFS (1.89 ± 0.11 vs. 3.16 ± 0.12 months, p <0.001) compared to PD group. The risk of HPD was higher than the risk of PD in patİents with a high PILE score (p:0.001). Conclusion In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. If prospective studies confirm our results, the PILE score may be a biomarker to differentiate HPD from PD.

Hyperprogressive disease during treatment with immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21664-e21664 ◽  
Author(s):  
Pablo Ayala de Miguel ◽  
Javier López Gallego ◽  
Itziar Gorospe García ◽  
Pablo René Rivera Vargas ◽  
Andrea Posada Restrepo ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Tumor Growth ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Eastern Cooperative Oncology Group ◽  
Hyperprogressive Disease ◽  
Metastatic Sites

e21664 Background: Hyperprogressive disease (HPD) is a new pattern of progressión during immunotherapy and is described as an acceleration of tumor growth during treatment with immune checkpoint inhibitors (ICI). The rate of HPD in advanced solid tumors remains unknown, but it has been reported in 9% to 29% of patients in two recent series. Our aim was to study prognostic factors of HPD. Methods: We collected data of 104 patients diagnosed of advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and December 2019. Several variables as clinical, tumour-related and therapeutical were included in the analysis. The variables were compared by chi-square and Fisher test, then we performed a multivariate logistic regression model to analyse the effects of the covariates, and finally we performed a Kaplan Meier survival analysis. We described HPD as disease progression at first evaluation with an increase in tumor growth rate exceeding 50%, according to Gustave Roussy criteria previously reported. Results: Cohort of 84 men and 20 women, median age of 67 years and 86% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 89% were active or ex-smokers and 11% had never smoked. 60% of patients had adenocarcinoma histology, 39% scamous and 1% had not otherwise specified (NOS) carcinoma histology. 3% of patients had III-B stage at the moment of start of immunotherapy, 37% M1a, 30% M1b and 30% M1c. 2 patients had driver mutations in EGFR gene. 41% of patients had unknown PDL1 status; 14% had no PDL1 expression, 14% low expression and 31% high expression. 78% of patients had progressed to prior line of treatment, while 22% were treatment-naive. Nine of 104 patients (8.7%) in our population developed HPD during treatment with ICI. HPD occured within the first two months of treatment in all 9 patients, and was associated with worse overall survival in the multivariate analysis by Cox regression (12.6 vs 2.6 months; HR 13.94, p < 0.001). The presence of 2 or more metastatic sites was related to the development of HPD in the multivariate analysis (HR 8.59, p = 0.026). Conclusions: The incidence of HPD in our population is concordant with previous report about this topic. As previously described by Ferrara et al, HPD was significantly associated with a high number of metastatic sites before start treatment with ICI and correlated with poor outcomes in patients with advanced NSCLC.

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