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.

Clinical implications of hyperprogression with immune checkpoint inhibitors in patients with head and neck squamous cell carcinoma (HNSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6034-6034 ◽  
Author(s):  
Panagiota Economopoulou ◽  
Nikolaos Spiridon Spathas ◽  
George Papaxoinis ◽  
Maria Anastasiou ◽  
Maria Gkotzamanidou ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Implications ◽  
Time To Treatment Failure ◽  
Early Progression ◽  
The Difference ◽  
Hyperprogressive Disease ◽  
Tumor Types

6034 Background: Hyperprogressive disease (HPD) refers to paradoxical acceleration of tumor growth kinetics (TGK) after initiation of treatment with anti- PD-1/PD- L1 agents and has been reported across tumor types in 4-29% of patients using different definitions. Preliminary data suggest that HPD might affect response to subsequent therapies. Methods: We compared TGK prior and TGK upon immunotherapy (IO) in 62 patients (pts) with recurrent/metastatic (R/M) HNSCC treated with PD-1/PD-L1 inhibitors. The TGK ratio (TGKR, ratio of tumor growth velocity before and upon treatment) was calculated. The first imaging assessment was performed 3 months (mo) after IO initiation. HPD was defined as 1. Radiological HPD (TGKR≥2) or 2. Clinical HPD (Disease-related rapid clinical deterioration post IO). Results: After median follow-up of 12.3 mo (range, 0.4-28.1), 43 pts progressed and 38 died. Median PFS was 2.8 mo (95%CI, 2.2-3.4) and median OS 8.6 mo (95%CI, 4.2-12.9). HPD was observed in 16 pts (25.8%), while 15 pts had early PD (Time to Treatment failure, TTF < 3 mo) and 31 late PD (TTF > 3mo). Among 16 pts with HPD, 11 had radiological HPD and 10 had clinical HPD. 4 pts had both clinical and radiological HPD. Pts with late PD had median OS 11.3 mo (95%CI, 9.3-13.3), those with early PD 5.2 mo (95%CI, 3.1-7.3 months) and those with HPD 5.1 mo (95%CI, 4.4-5.9) (p < 0.005). Regarding post-progression OS, pts with late PD had median 11.3 mo (95%CI 0-22.8), those with early PD 2.5 mo (95%CI 0.6-4.4) and those with HPD 4.2 mo (95%CI 1.7-6.7) (p = 0.001). Pts with HPD had a trend for longer median post-progression OS compared to pts with early PD (p = 0.121). Median PFS with chemotherapy after immunotherapy failure was 3.0 mo (95%CI 2.4-3.6) for pts with late PD, 2.1 mo (95%CI 0.9-3.4) for pts with early PD and 6.1 mo (95%CI 3.0-9.3) for those with HPD (p = 0.040). HPD was associated with longer median PFS with chemotherapy compared to pts with early PD (p = 0.016), while the difference in median PFS with chemotherapy between pts with HPD and late progressors was non-statistically significant (p = 0.260). Conclusions: Radiological or clinical HPD was observed in 25.8% of patients with R/M HNSCC treated with IO. Early progression to immunotherapy is an important predictor of short survival, while HPD was associated with improved PFS to subsequent chemotherapy.

scholarly journals Dramatic Response in a Patient with Metastatic Gastric Cancer Using Trifluridine/Tipiracil after Rapid Disease Progression while on Nivolumab

2020 ◽  
Vol 13 (3) ◽  
pp. 1381-1386
Author(s):  
Kazuki Nozawa ◽  
Yukiya Narita ◽  
Waki Hosoda ◽  
Kei Muro
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Pattern ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Laboratory Data ◽  
Metastatic Gastric Cancer ◽  
Cytotoxic Agents ◽  
Hyperprogressive Disease

The introduction of immune checkpoint inhibitors has redefined the treatment strategy and changed the way tumor assessments are made because of its response pattern. Studies have suggested that initiating chemotherapy after checkpoint inhibitors may have high anti-tumor activity in some cancer types. This response pattern has not been reported in patients with gastric cancer, and particularly for the combination of trifluridine/tipiracil. A 69-year-old man presented at follow-up for metastatic gastric cancer being treated with nivolumab, an anti-PD-1 antibody. Computed tomography of the liver showed a rapid 4-fold growth of the metastasis compared with baseline measurements taken while receiving paclitaxel and ramucirumab. It met the definition of a phenomenon called hyperprogressive disease. Nivolumab was discontinued, and he was switched to trifluridine/tipiracil. The liver metastasis was shrunk markedly after 2 months with improvement in his performance status and laboratory data. Sequential therapy starting with immune checkpoint inhibitors followed by cytotoxic agents such as trifluridine/tipiracil may have an apparent efficacy in gastric cancer even though prior immunotherapy demonstrates hyperprogressive disease.

A plasma miRNA signature classifier identifies PD-L1 ≥ 50% NSCLC nonresponders to immune checkpoint inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9096-9096
Author(s):  
Claudia Proto ◽  
Arsela Prelaj ◽  
Carla Verri ◽  
Diego Signorelli ◽  
Giuseppe Lo Russo ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Single Agent ◽  
Risk Level ◽  
Fisher Exact Test ◽  
Molecular Test ◽  
Ecog Performance Status

9096 Background: A sizable proportion of PD-L1≥50% NSCLC patients (pts) do not respond to single agent immune checkpoint inhibitors (ICI) and no biomarker is able to identify non responders. A three levels plasma microRNA signature classifier (MSC), reflecting an immunosuppressive profile of immune cell subsets, has already shown its ability to identify pts treated with ICI with a worse prognosis independently from PD-L1 expression. Aim of this trial is to prospectively test the ability of MSC to identify at diagnosis PD-L1≥50% non responders to ICI. Methods: we prospectively collected baseline plasma samples from 41 consecutive advanced EGFR/ALK/ROS1 wild-type NSCLC pts with PD-L1 TPS ≥50% treated with ICI as first (n = 28) or further line treatment to run the MSC molecular test. Pts were stratified in high (H) vs intermediate/low (I/L) risk levels. Overall response rate (ORR) and the relative risk of response (RR) were evaluated by 2x2 contingency table using Fisher exact test. Cox proportional hazard models were used to define crude and adjusted hazard ratio (HR). Results: According to RECIST 1.1 criteria, 14 (34%) pts respond to ICIs. With a global median follow-up of 9.8 months, median progression free survival (PFS) and overall survival (OS) were 7.9 months and not reached, respectively. Ten (24%) NSCLC pts were MSC H risk level. ORR was 0% in MSC H vs 45% in MSC I/L risk pts (RR = 0.10; 95%CI = 0.00-0.90; p = 0.0080). Median PFS was 11.4 months for MSC I/L pts vs 2.3 months for MSC H risk (HR = 0.26 95%CI = 0.11-0.62; p = 0.0021). Median OS was not reached for MSC I/L vs 2.7 months for MSC H risk pts (HR = 0.17 95%CI = 0.06-0.48; p = 0.0008). Data remained significant adjusting for age, sex, pack-years and ECOG performance status at the baseline: PFS HR = 0.24 (95%CI = 0.09-0.66; p = 0.0054) and OS HR = 0.15 (95%CI = 0.05-0.51; p = 0.0023). Conclusions: plasma MSC shows promising results for treatment selection with ICI. So far, MSC is the only molecular test able to identify a group of NSCLC pts with PD-L1≥50% who do not respond to single agent immunotherapy. Ongoing trials are validating these results and testing the possible predictive effect of MSC in chemotherapy plus immunotherapy combinations.

Managing viral hepatitis in cancer patients under immune checkpoint inhibitors: should we take the risk?

Immunotherapy ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 409-418
Author(s):  
Stijn J De Keukeleire ◽  
Tijl Vermassen ◽  
Zahra M Nezhad ◽  
Tessa Kerre ◽  
Vibeke Kruse ◽  
...  
Keyword(s):  
Viral Hepatitis ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Chronic Viral Hepatitis ◽  
Viral Clearance ◽  
Viral Reactivation ◽  
Immune Checkpoints

More patients with chronic hepatitis B and C infection are being exposed to immune checkpoint inhibitors (ICIs), but the safety and efficacy of ICIs in patients with chronic viral hepatitis are still poorly described. To explore this interaction, we identified eight studies of cancer patients with viral hepatitis treated with one or more ICIs, formally assessed tumor responses and safety by grading liver dysfunction. ICIs appear to be relatively safe in HBV/HCV-infected patients, and hepatitis related to viral reactivation is rare. In some patients, viral load regressed during ICI treatment, so immune checkpoints may play a role in viral clearance. HBV/HCV do not appear to be a contraindication to ICIs, although careful clinical and biochemical follow-up is recommended and, whenever necessary, antiviral therapy commenced.

Abstract 14600: Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Charlotte Lee ◽  
Zsofia D Drobni ◽  
Amna Zafar ◽  
Raza M Alvi ◽  
Sean P Murphy ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Autoimmune Disease ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Cardiovascular Events ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Significant Difference

Introduction: The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients. Methods: This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis. Results: 93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none, P =0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%, P =0.04), PCI (0 vs. 0.5%, P =1), CABG (0. vs. 0.5%, P =1), stroke (0 vs. 0%), TIA (0 vs. 0.5%, P =1), DVT (5.4 vs. 2.2%, P =0.17), PE (1.1 vs. 4.8%, P =0.17), and myocarditis (2.2 vs. 1.1%, P =0.60). There was an increased rate of pneumonitis (14 vs. 4%, P <0.001) and skin toxicity (16 vs. 0%, P <0.001). Conclusions: Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.

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 Efficacy of immune checkpoint inhibitors for in-transit melanoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000440 ◽  
Author(s):  
Emilia Nan Tie ◽  
Julia Lai-Kwon ◽  
Michael Alexander Rtshiladze ◽  
Lumine Na ◽  
James Bozzi ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Mek Inhibitor ◽  
Disease Recurrence ◽  
In Transit

BackgroundThe efficacy of immune checkpoint inhibitors (ICI) in metastatic melanoma is well established. However, there are limited data regarding their efficacy in in-transit melanoma (ITM). This study assessed the efficacy of ICI in patients with ITM.MethodsA retrospective review of patients with ITM commenced on an ICI between March 2013 and February 2018 at three tertiary centers in Australia. Patients were excluded if they had previous or synchronous distant metastases. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were based on a composite of radiological and clinical assessments.ResultsFifty-four patients were included: 27 (50%) female; median age 75 (range 26–94); 12 (22%) stage IIIB, 40 (74%) stage IIIC and 2 (4%) stage IIID; 10 (19%) BRAF mutant. Forty (74%) received single-agent anti-PD-1 (pembrolizumab or nivolumab), 8 (15%) single agent anti-CTLA-4 (ipilimumab), 5 (9%) combination anti-PD-1/anti-CTLA-4 (ipilimumab and nivolumab or pembrolizumab) and 1 (2%) combination anti-PD-L1 (atezolizumab) and MEK inhibitor (cobimetinib). The median follow-up was 15 months (2–46).ORR to ICI was 54%: 14 (26%) complete responses; 15 (28%) partial responses; 9 (17%) stable disease; 16 (30%) progressive disease. Thirteen (46%) responders had only one ITM lesion. ORR was 58% for single-agent anti-PD-1, 38% for single-agent anti-CTLA4 and 40% for anti-PD-1/anti-CTLA-4. The median PFS was 11.7 months (6.6-not reached). 1-year and 2-year PFS were 48% and 39%, respectively,. Fourteen progressed locoregionally and 11 progressed distantly. The median OS was not reached. 1-year and 2-year OS were 85% and 63%, respectively. No clinicopathological features were associated with ORR.Conclusions and relevanceICI produce objective responses in ITM and should be considered in patients with unresectable ITM or disease recurrence.

scholarly journals ePROs in the follow-up of cancer patients treated with immune checkpoint inhibitors: a retrospective study

2019 ◽  
Vol 145 (3) ◽  
pp. 765-774 ◽  
Author(s):  
Sanna Iivanainen ◽  
Tuomo Alanko ◽  
Katriina Peltola ◽  
Teemu Konkola ◽  
Jussi Ekström ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Immune Checkpoint Inhibitor Use Near the End of Life Is Associated With Poor Performance Status, Lower Hospice Enrollment, and Dying in the Hospital

2019 ◽  
Vol 37 (3) ◽  
pp. 179-184 ◽  
Author(s):  
Chad Glisch ◽  
Yuya Hagiwara ◽  
Stephanie Gilbertson-White ◽  
Yubo Gao ◽  
Laurel Lyckholm
Keyword(s):  
End Of Life ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Inhibitor Treatment

Background: Immune checkpoint inhibitors have changed the landscape of cancer care by increasing progression-free and overall survival in some patients with cancer. We evaluated use and variables contributing to immune checkpoint inhibitor treatment near the end of life. Methods: We studied 157 patients who received immune checkpoint inhibitors and died between January 2015 and December 2018. All patients had a palliative care consult any time between starting an immune checkpoint inhibitor and death. Univariate and multivariate models were used to examine variables related to immune checkpoint inhibitor use near the end of life. Results: Among 157 patients studied, 42 (27%) received a dose of immune checkpoint inhibitor in the last 30 days of life. Those who received treatment in the last 30 days of life had lower hospice enrollment (19 [45%] vs 78 [69%], P = .007) and higher rates of dying in the hospital (23 [56%] vs 33 [29%], P = .002). The percentage of patients with Eastern Cooperative Oncology Group (ECOG) ≥3 at the time of last immune checkpoint inhibitor dose was higher in the group that received immune checkpoint inhibitor treatment in the last 30 days of life (11 [26%] vs 9 [8%], P = .003). Lack of traditional chemotherapy after immune checkpoint inhibitor, ECOG ≥3, and lack of hospice enrollment were independently associated with receiving immune checkpoint inhibitor in the last 30 days of life. Conclusion: Immune checkpoint inhibitor use in the last 30 days of life is common and associated with poor performance status, lower hospice enrollment, and dying in the hospital.

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