Durable response after immunotherapy discontinuation for delayed and severe immune-related adverse event: a case report

Immunotherapy ◽  
2021 ◽  
Author(s):  
Guido Pesola ◽  
Veronica Murianni ◽  
Sara Elena Rebuzzi ◽  
Giuseppe Luigi Banna ◽  
Luigi Cerbone ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Renal Cell Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Case ◽  
Renal Toxicity ◽  
Checkpoint Inhibitors ◽  
Durable Response ◽  
Disease Outcomes ◽  
Clinical Benefits ◽  
Metastatic Rcc

Recent studies have shown that immune-related adverse events (irAEs), occurring even after the discontinuation of immune checkpoint inhibitors (ICIs), may be associated with favorable disease outcomes, particularly in patients with melanoma and lung cancer. However, a few clinical cases have been described on the correlation between irAEs and ICIs efficacy in renal cell carcinoma (RCC) patients. This study reports the clinical case of a metastatic RCC patient who has experienced severe immune-related renal toxicity after 19 months of nivolumab use. Despite immunotherapy discontinuation, the patient has maintained clinical benefit and disease progression-free for 3 years. We examined the correlation between the occurrence and the severity of irAEs, treatment discontinuation and clinical benefits. The evidence on ICI retreatment following ICI discontinuation due to irAEs was also reviewed.

scholarly journals Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors

2020 ◽  
Vol 38 (27) ◽  
pp. 3088-3094 ◽  
Author(s):  
Anita Gul ◽  
Tyler F. Stewart ◽  
Charlene M. Mantia ◽  
Neil J. Shah ◽  
Emily Stern Gatof ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Rcc

PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

scholarly journals Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4931 ◽  
Author(s):  
Andrea Bianco ◽  
Fabio Perrotta ◽  
Giusi Barra ◽  
Umberto Malapelle ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
T Cell Subsets ◽  
Durable Response ◽  
Lung Cancer Treatment ◽  
The Impact

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

scholarly journals Treatment of Metastatic Renal Cell Carcinoma: Latest Evidence and Ongoing Challenges

2018 ◽  
Vol 11 ◽  
pp. 117956111876575 ◽  
Author(s):  
Pedro Aguiar ◽  
Tiago Costa de Pádua ◽  
Carmelia Maria Noia Barreto ◽  
Auro del Giglio
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Synergistic Activity ◽  
Antiangiogenic Drugs ◽  
Metastatic Rcc

Recently, the development of antiangiogenic drugs has changed the therapy for metastatic renal cell carcinoma (RCC). As a result, the survival of individuals with advanced RCC has more than doubled. The median overall survival improved from 12 months during the cytokines era to near 30 months with antiangiogenic drugs. In this decade, the advent of immune checkpoint inhibitors showed enthusiastic results and is the new standard of care for patients with metastatic RCC previously treated with antiangiogenic drugs. The combination of immune checkpoint inhibitors plus antiangiogenic drugs may have a synergistic activity. As a result, current studies investigate the combination for treatment-naïve patients. This may potentially change clinical practice. In this article, we will highlight new therapeutic options available and agents or combinations that are being investigated for metastatic RCC.

scholarly journals Combination of computed tomography imaging-based radiomics and clinicopathological characteristics for predicting the clinical benefits of immune checkpoint inhibitors in lung cancer

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Bin Yang ◽  
Li Zhou ◽  
Jing Zhong ◽  
Tangfeng Lv   ◽  
Ang Li ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Regression Analysis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinicopathological Characteristics ◽  
Ct Images ◽  
Clinical Benefits ◽  
Nsclc Patients

Abstract Background In this study, we tested whether a combination of radiomic features extracted from baseline pre-immunotherapy computed tomography (CT) images and clinicopathological characteristics could be used as novel noninvasive biomarkers for predicting the clinical benefits of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Methods The data from 92 consecutive patients with lung cancer who had been treated with ICIs were retrospectively analyzed. In total, 88 radiomic features were selected from the pretreatment CT images for the construction of a random forest model. Radiomics model 1 was constructed based on the Rad-score. Using multivariate logistic regression analysis, the Rad-score and significant predictors were integrated into a single predictive model (radiomics nomogram model 1) to predict the durable clinical benefit (DCB) of ICIs. Radiomics model 2 was developed based on the same Rad-score as radiomics model 1.Using multivariate Cox proportional hazards regression analysis, the Rad-score, and independent risk factors, radiomics nomogram model 2 was constructed to predict the progression-free survival (PFS). Results The models successfully predicted the patients who would benefit from ICIs. For radiomics model 1, the area under the receiver operating characteristic curve values for the training and validation cohorts were 0.848 and 0.795, respectively, whereas for radiomics nomogram model 1, the values were 0.902 and 0.877, respectively. For the PFS prediction, the Harrell’s concordance indexes for the training and validation cohorts were 0.717 and 0.760, respectively, using radiomics model 2, whereas they were 0.749 and 0.791, respectively, using radiomics nomogram model 2. Conclusions CT-based radiomic features and clinicopathological factors can be used prior to the initiation of immunotherapy for identifying NSCLC patients who are the most likely to benefit from the therapy. This could guide the individualized treatment strategy for advanced NSCLC.

scholarly journals The Role of Obesity in Renal Cell Carcinoma Patients: Clinical-Pathological Implications

2019 ◽  
Vol 20 (22) ◽  
pp. 5683 ◽  
Author(s):  
Gaetano Aurilio ◽  
Francesco Piva ◽  
Matteo Santoni ◽  
Alessia Cimadamore ◽  
Giulia Sorgentoni ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Renal Cell Carcinoma ◽  
Adipose Tissue ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Rcc

Obesity is a well-known risk factor for renal cell carcinoma (RCC) development. However, the RCC–obesity link has not been fully addressed when considering a comprehensive scenario starting from pathogenetic aspects through pathological issues up to the outcome of medical treatment. We therefore conducted an electronic PubMed search using keywords “obesity”, “body mass index”, “overweight”, “renal cell carcinoma/kidney cancer”, “medical treatment”, “targeted therapy”, and “immunotherapy/immune checkpoint inhibitors”. The selected data supported a crosstalk between adipose tissue (adipocytes and other white adipose tissue cells) and cancer cells inducing several signaling pathways that finally stimulated angiogenesis, survival, and cellular proliferation. Accurate sampling of renal sinus fat correlated with a prognostic value. Retrospective clinical evidence in metastatic RCC patients with higher body mass index (BMI) and treated with targeted therapies and/or immune checkpoint inhibitors showed advantageous survival outcomes. Therefore, obesity may influence the course of RCC patients, although the interplay between obesity/BMI and RCC warrants a large prospective confirmation. We are therefore still far from determining a clear role of obesity as a prognostic/predictive factor in metastatic RCC patients undergoing targeted therapy and immunotherapy.

Tumor LAG-3 and NY-ESO-1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer

2020 ◽  
Author(s):  
Eun Hee Jung ◽  
Hee Ryung Jang ◽  
Se Hyun Kim ◽  
Koung Jin Suh ◽  
Yu Jung Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
National University ◽  
Clinical Benefits ◽  
Seoul National University

Abstract Background Immune checkpoint inhibitors (ICIs) are an established treatment for non-small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested that NY-ESO-1 and LAG-3 could be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of NY-ESO-1 and LAG-3 expression in NSCLC. Methods We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti-PD-1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum-based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY-ESO-1, LAG-3, and PD-L1 expression, whose ability to predict progression-free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values. Results NY-ESO-1 or LAG-3 expression was detected in all tumor samples from patients with high PD-L1 expression and was significantly associated with favorable patient outcomes, unlike PD-L1 expression. Patients whose tumors expressed both NY-ESO-1 and LAG-3 had a high DCB rate and those with triple-positive PD-L1, LAG-3, and NY-ESO expression had a superior median OS and PFS compared to those in patients with triple-negative expression. Furthermore, LAG-3 and NY-ESO-1 co-expression was an independent predictor of both PFS and OS, while LAG-3 displayed a good NPV. Conclusion Therefore, patients with NSCLC who co-express NY-ESO-1 or LAG-3 with PD-L1 exhibit greater DCBs and improved long-term survival following anti-PD-1 therapy. Moreover, NY-ESO-1 and LAG-3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.

scholarly journals Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results

2021 ◽  
Vol 11 (3) ◽  
pp. 206
Author(s):  
Teresa Troiani ◽  
Stefania Napolitano ◽  
Gabriella Brancaccio ◽  
Valentina Belli ◽  
Annarita Nappi ◽  
...  
Keyword(s):  
Melanoma Cell Line ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Case ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Durable Response ◽  
Melanoma Patients ◽  
New Treatment ◽  
First Time

Melanoma is the most lethal form of skin cancer and its incidence is growing worldwide. In the last ten years, the therapeutic scenario of this disease has been revolutionized by the introduction of targeted therapies and immune-checkpoint inhibitors. However, in patients with many lesions and bulky tumors, in which surgery is no longer feasible, there is a need for new treatment options. Here we report, for the first time to our knowledge, a clinical case where a melanoma patient harboring the SMO p.Gln216Arg mutation has been treated with imiquimod, showing a complete and durable response. To better explain this outstanding response to the treatment, we transfected a melanoma cell line (MeWo) with the SMO p.Gln216Arg mutation in order to evaluate its role in response to the imiquimod treatment. Moreover, to better demonstrate that the antitumor activity of imiquimod was due to its role in suppressing the oncogenic SMO signaling pathway, independently of its immune modulating function, an in vivo experiment has been performed. This clinical case opens up a new scenario for the treatment of melanoma patients identifying a new potentially druggable target.

scholarly journals Atypical Response Patterns in Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors—Navigating the Radiologic Potpourri

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1689
Author(s):  
Alvin Wong ◽  
Balamurugan Vellayappan ◽  
Lenith Cheng ◽  
Joseph J. Zhao ◽  
Vaishnavi Muthu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Full Range ◽  
Late Response ◽  
Response Patterns ◽  
Durable Response

Background: Atypical response patterns have been a topic of increasing relevance since the advent of immune checkpoint inhibitors (ICIs), challenging the traditional RECIST (Response Evaluation Criteria in Solid Tumors) method of tumor response assessment. Newer immune-related response criteria can allow for the evolution of radiologic pseudoprogression, but still fail to capture the full range of atypical response patterns encountered in clinical reporting. Methods: We did a detailed lesion-by-lesion analysis of the serial imaging of 46 renal cell carcinoma (RCC) patients treated with ICIs with the aim of capturing the full range of radiologic behaviour. Results: Atypical response patterns observed included pseudoprogression (n = 15; 32.6%), serial pseudoprogression (n = 4; 8.7%), dissociated response (n = 22; 47.8%), abscopal response (n = 9; 19.6%), late response (n = 5; 10.9%), and durable response after cessation of immunotherapy (n = 2; 4.3%). Twenty-four of 46 patients (52.2%) had at least one atypical response pattern and 18 patients (39.1%) had multiple atypical response patterns. Conclusions: There is a high incidence of atypical response patterns in RCC patients receiving ICIs and the study contributes to the growing literature on the abscopal effect. The recognition of these interesting and overlapping radiologic patterns challenges the oncologist to tweak treatment options such that the clinical benefits of ICIs are potentially maximized.

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