The impact of frailty on the occurrence of immune-related adverse events in older patients with advanced melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24028-e24028
Author(s):  
Cheryl P. Bruijnen ◽  
Josephine J Koldenhof ◽  
Erwin H.J. Tonk ◽  
Rik Jasper Verheijden ◽  
Frederiek van den Bos ◽  
...  
Keyword(s):  
Adverse Events ◽  
Older Patients ◽  
Checkpoint Inhibitors ◽  
Advanced Melanoma ◽  
Frail Patients ◽  
Systemic Corticosteroids ◽  
Life Threatening ◽  
Major Increase ◽  
Grade 3 ◽  
The Impact

e24028 Background: Immune checkpoint inhibitors (ICIs) have changed the melanoma treatment landscape by inducing durable responses and significantly improving survival. ICI can cause immune-related adverse events (irAES) ranging from mild to life threatening. Clinical trials have not shown major increase of irAES in older patients when compared to younger patients. However, older patients have been underrepresented and were relatively fit in these trials. In this study, we assessed the occurrence of irAEs treated with systemic corticosteroids and/or leading to treatment discontinuation (relevant irAEs) in older patients with melanoma and, if relevant irAEs occurred more often in frail patients, as assessed with the Geriatric 8 (G8). Methods: Patients ≥70 years diagnosed with advanced melanoma, about to start with ICI, and screened with a G8, were enrolled in this prospective observational study. Patients were classified according to the G8 score as “fit” (G8 score >14) or “frail” (G8 score ≤14). Toxicity was scored according to CTCAE v4.03. Primary outcome was occurrence of relevant irAEs in “fit” and “frail” patients. Secondary outcomes were the occurrence of irAEs any grade and severe irAE (grade ≥3). Results: In total, 49 patients were included for statistical analyses. Thirty-three patients were classified fit according to the G8 and, 16 patients were frail. Relevant irAEs occurred statically significantly more often in in frail patients: 12 (75%) versus 15 patients (46%) ( p=0.05). In addition, more irAEs grade ≥3 were reported in frail patients, although not significant: 7 (44%) versus 8 patients (25%) ( p= 0.11). Conclusions: Frailty, classified by the G8, is associated with the occurrence of relevant irAEs in the older patient with advanced melanoma. These data need to be confirmed in larger series.

Toxicity, response, and survival in older adults with metastatic melanoma treated with checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9544-9544
Author(s):  
Nienke A De Glas ◽  
Esther Bastiaannet ◽  
Frederiek van den Bos ◽  
Simon Mooijaart ◽  
Astrid Aplonia Maria Van Der Veldt ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Metastatic Melanoma ◽  
Older Patients ◽  
Regression Models ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Toxicity Response ◽  
Grade 3 ◽  
The Impact

9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ≥65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ≥3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ≥3 toxicity did not increase with age, comorbidity or WHO performance status, in patients treated with monotherapy (anti-PD1 or ipilimumab) or combination treatment. However, patients aged ≥75 were admitted more frequently and discontinued treatment due to toxicity more often. Six months-response rates were similar to previous randomized trials (40.3% and 43.6% in patients aged 65-75 and ≥75 respectively for anti-PD1 treatment) and were not affected by age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity, but age, comorbidity and WHO performance status were associated with overall survival in multivariate analyses. Conclusions: Toxicity, response and melanoma-specific survival were not associated with age or comorbidity status. Treatment with immunotherapy should therefore not be omitted solely based on age or comorbidity. However, the impact of grade I-II toxicity in older patients deserves further study as older patients discontinue treatment more frequently and receive less treatment cycles.[Table: see text]

Impact of radiotherapy on risk of adverse events in patients receiving immunotherapy: A U.S. Food and Drug Administration pooled analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3018-3018
Author(s):  
Mitchell Steven Anscher ◽  
Shaily Arora ◽  
Chana Weinstock ◽  
Rachael Lubitz ◽  
Anup Amatya ◽  
...  
Keyword(s):  
Adverse Events ◽  
Inflammatory Responses ◽  
Checkpoint Inhibitors ◽  
Pooled Analysis ◽  
Hematologic Toxicity ◽  
Pooled Data ◽  
Advanced Malignancies ◽  
Prospective Trials ◽  
Grade 3 ◽  
The Impact

3018 Background: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of multiple advanced malignancies. Radiotherapy (RT) has been used in combination with ICIs to activate tumor-specific T cell responses, and RT also promotes non-specific acute and chronic inflammatory responses both locally and systemically. More than 50% of patients receive RT at some point during their course of cancer therapy, and relatively little information is available pertaining to the impact of RT, if any, on the risk of adverse events (AEs) in patients receiving ICIs. Methods: Pooled data from prospective trials of ICIs submitted to the FDA in initial or supplemental BLAs or NDAs through 12/2019 were included (N=66). Trials from applications that were withdrawn or not approved were not included. Patients were subdivided by whether or not radiotherapy was administered at any time during the course of their cancer treatment. AEs common to both ICI treatment and RT were identified to focus on the following reactions: neutropenia, thrombocytopenia, colitis, hepatitis, pneumonitis, and myocarditis. Descriptive statistics were used to examine AEs associated with the use of radiation and ICIs. Results: A total of 25,836 patients were identified, of which 9087 (35%) received RT and 16,749 (65%) did not. Radiation was associated with similar rates of AEs overall with numerically higher hematologic toxicities and pneumonitis and numerically lower colitis, hepatitis and myocarditis (Table). Patients receiving RT were more likely to experience Grade 3-5 hematologic toxicities compared to those not receiving RT. Conclusions: To our knowledge, this is the largest report of AE risk associated with the use of radiation and ICIs. Our results show that the incidence of hematologic toxicity and pneumonitis in patients receiving RT may be slightly higher. Analysis to determine comparability of baseline demographic characteristics, comprehensive AE profile, and timing of RT is underway. [Table: see text]

scholarly journals Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2365
Author(s):  
Charline Lafayolle de la Bruyère ◽  
Pierre-Jean Souquet ◽  
Stéphane Dalle ◽  
Pauline Corbaux ◽  
Amélie Boespflug ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Glucocorticoid Administration ◽  
Grade 3 ◽  
The Impact

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.

Assessment of hospitalization rates for immune-related adverse events with immune checkpoint inhibitors

2020 ◽  
pp. 107815522096890
Author(s):  
Laura Nice ◽  
Ryan Bycroft ◽  
Xiaoyong Wu ◽  
Shesh N Rai ◽  
Lindsay Figg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Median Length ◽  
Number Of Patients ◽  
Grade 3 ◽  
The Impact

Introduction Immune checkpoint inhibitors (ICIs) have become the standard of care in many cancer types. As the number of patients receiving ICIs for various cancers continues to expand, patients and practitioners should be aware of potentially severe immune-related adverse events (irAEs). Despite reports of the incidence of grade 3/4 toxicities, the proportion of patients whose symptoms were clinically severe enough to warrant hospitalization for adverse event management is unknown. Methods This single center, retrospective, observational study was designed to determine the impact of irAEs on patients and the hospital. Patients who started ICIs from May 2016 through May 2019 for melanoma or lung cancer were included. The primary outcome was incidence of hospitalization for irAE. Secondary outcomes included median length of hospitalization, time to onset of irAE, rates of hospitalization for irAE per each checkpoint inhibitor regimen, organ system affected, progression free survival, and overall survival. Results Of 384 patients with melanoma or lung cancer, 27 (7%) were hospitalized at our institution for an irAE. The most common irAE leading to hospitalization was colitis for patients with melanoma and pneumonitis for patients with lung cancer. The median length of stay across all hospitalizations was 10 days. Twenty-five patients required the use of corticosteroids while hospitalized, while eight of these patients required second line irAE treatment. For the total patient population, 34.7% experienced a grade 1/2 irAE and 13.1% experienced a grade 3/4 irAE. Conclusion Our cohort of patients experienced similar rates irAEs as reported in clinical trials and published reports.

scholarly journals Impact of Immune-Related Adverse Events on Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽  
2021 ◽  
pp. 1-13
Author(s):  
Kennedy Yao Yi Ng ◽  
Sze Huey Tan ◽  
Jack Jie En Tan ◽  
Desiree Shu Hui Tay ◽  
Ailica Wan Xin Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multivariable Analysis ◽  
Primary Study ◽  
Advanced Hepatocellular Carcinoma ◽  
Systemic Corticosteroids ◽  
Grade 3

<b><i>Introduction:</i></b> Development of immune-related adverse events (irAEs) has been associated with enhanced efficacy with the use of immune checkpoint inhibitors (ICIs). It remains unknown whether such an association exists in advanced hepatocellular carcinoma (aHCC). This study aims to evaluate the association between irAEs and ICI efficacy in patients with aHCC. <b><i>Methods:</i></b> We performed a retrospective cohort study on patients with aHCC who received at least one dose of an ICI between May 2015 and November 2019 at the National Cancer Centre Singapore. The primary study objectives were to compare the overall survival (OS) and progression-free survival (PFS) between patients with and without irAEs. Complementary multivariable landmark analyses were performed at the 6-week and 12-week landmarks. Data cutoff was December 31, 2020. <b><i>Results:</i></b> One hundred and sixty-eight patients were included. Median age was 69 years, 85.7% were male, 57.7% had hepatitis B infection, 60.7% had ECOG 0, and 78.0% had Child-Pugh A liver cirrhosis. 82.7% received ICI monotherapy, while 17.3% received ICI in combination. Development and severity of irAE were correlated with survival. The median PFS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 8.5 versus 3.6 versus 1.3 mths (<i>p</i> &#x3c; 0.001). The median OS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 26.9 versus 14.0 versus 4.6 mths (<i>p</i> &#x3c; 0.001). Patients with ≥2 irAEs had a significantly longer OS on multivariable analysis (adjusted hazard ratio [aHR]0.35, <i>p</i> &#x3c; 0.001). The presence of grade ≥3 irAEs was associated with a significantly longer OS on the multivariable analysis at the 6-week landmark (aHR0.34, <i>p</i> = 0.030) and 12-week landmark (aHR0.28, <i>p</i> = 0.011). The use of systemic corticosteroids in patients with irAE was associated with a trend toward a longer OS (20.7 vs. 14.3 mths, <i>p</i> = 0.064). <b><i>Conclusion:</i></b> Our study suggests that the presence of all-grade irAEs may be a potential prognostic biomarker in patients with aHCC treated with ICI. Patients with more severe irAEs and multisystem involvement have better prognosis. The prompt use of systemic corticosteroids to treat patients with irAEs is key to ensure the best long-term outcomes for these patients.

scholarly journals Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

2021 ◽  
Vol 13 ◽  
pp. 175883592199298
Author(s):  
Orthi Shahzad ◽  
Nicola Thompson ◽  
Gerry Clare ◽  
Sarah Welsh ◽  
Erika Damato ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Simple Algorithm ◽  
Cancer Therapeutics ◽  
Management Algorithm ◽  
Ocular Symptoms ◽  
Systemic Corticosteroids ◽  
Permanent Loss

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

Age affects the efficacy of immune checkpoint inhibitors in patients with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2638-2638
Author(s):  
Yongjie Wang ◽  
Ronghua Yang ◽  
Dong Wang ◽  
Donghua Zhao ◽  
Peng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Older Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Sign Test ◽  
Patients With Cancer ◽  
The Impact ◽  
Effect Of Age

2638 Background: Immune checkpoint inhibitors (ICIs), such as programmed death(ligand)1 (PD-(L)1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, have dramatic effects on treatment in patients with various malignancies. High tumor mutation burden (TMB) is predictive of clinical response to ICI in multiple cancer types. Although age-related immune dysfunction might induce difference on the efficacy of ICIs between younger and older patients, the potential effect of age on the efficacy of ICIs remains little known and controversial. Herein, we aimed to analysis the association between age and the efficacy of ICIs based on MSKCC cohort. Methods: We screened out 1661 patients having complete information with advanced cancer, whose tumors underwent next-generation sequencing (NGS) detection and who were treated with at least one dose of ICI in MSKCC cohort. All patients were divided into two groups according to age, the younger group (age ≤50-year old) and the older group (age > 50-year old). We further analyzed the differences in overall survival (OS) and TMB between the two groups. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated via Cox regression model for OS and P-values were calculated via the Wilcoxon sign test for TMB. We analyzed the effect of age on ICI in lung cancer using the same way. Results: In 1661 patients with cancer in our study, 312 (19%) younger and 1349 (81%) older patients were found. The pooled HRs for OS was 1.28 (95% CI: 1.09-1.52) in younger group compared with older group. In 1661 patients with cancer, there was 350 (21%) patients with lung cancer, including 30 (9%) younger and 320 (91%) older patients. The pooled HRs for OS was 1.45 (95% CI: 0.95-2.23) in younger group compared with older group in lung cancer. In addition, TMB in older group was higher than in younger group and significant difference of TMB was found via the Wilcoxon sign test (p = 2.6e-10) between the two groups, especially in lung cancer (p = 1e-4). Conclusions: Our study assessed the impact of age on the efficacy of ICIs using the threshold of 50 years old for the first time and we founded that patients in older group had higher TMB and longer OS than younger group.

Comprehensive ambulatory monitoring during immunotherapy in patients with advanced melanoma: A prospective trial (CAMP-IT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS1589-TPS1589
Author(s):  
Milan Kos ◽  
Laurien Buffart ◽  
Jan Willem de Groot ◽  
Hans Westgeest ◽  
Wouter Dercksen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Real Time ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Ambulatory Monitoring ◽  
Vital Signs ◽  
Advanced Melanoma ◽  
Smartphone App ◽  
Survival Outcomes ◽  
Activity Data

TPS1589 Background: The emergence of immune checkpoint inhibitors has improved survival outcomes for patients with advanced melanoma. However, these treatment modalities are also associated with specific immune-related toxicities. These are often reversible after prompt recognition and initiation of appropriate management, but can result in severe morbidity and hamper health-related quality of life (HRQoL) if left undetected. Hence, accurate and regular monitoring of these patients is critical. Recent advances in mHealth technologies and the rapidly expanding armamentarium of wearable devices allow for real-time objective (vital signs and physical activity) data and patient-reported outcome measurement (PROMs) collection and, hence, serve this purpose. We hypothesize that collection of real-time objective data adds to the early detection of disease- and treatment-related adverse events. The primary objective of this study is to determine the feasibility of collecting real-time PROMs, vital signs, and physical activity data in advanced melanoma patients receiving immunotherapy using a comprehensive ambulatory monitoring platform (CAMP) that consists of a smartphone app, activity monitor, digital thermometer, and online dashboard for physicians. Methods: In this prospective multi-center trial, patients (n = 50) with advanced melanoma, scheduled to receive immunotherapy with immune checkpoint inhibitors, and with access to a smartphone are eligible for inclusion. Consenting patients will be asked to wear a FitBit Versa 2.0 during waking hours, collect daily temperature measurements using a Withings Smart Temporal thermometer, and answer weekly toxicity questionnaires (NCI PRO-CTCAE) using the smartphone app for the duration of the study (12 weeks). Primary outcome is feasibility in terms of (i) participation rates, (ii) wear-time, (iii) compliance rates with in-app questionnaires and temperature measurements, and (iv) satisfaction with the platform. Secondary exploratory outcomes include associations between CAMP-derived parameters and clinical outcomes: performance status (PS), HR-QoL scores (EORTC QLQ-C30 questionnaire), unplanned hospitalizations, physician-assessed adverse events, and 1-year survival outcomes. PS and HR-QoL will be rated at baseline, mid-study, and end-of-study. The occurrence of adverse events will be documented up to 12 months from baseline. Survival outcomes will be compared to a propensity score matched group from the Netherlands Cancer Registry. Accrual has started in February 2021. Clinical trial information: NL8827.

Does the primary tumour location affect the prognosis of patients with colorectal cancer peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haipeng Chen ◽  
Sicheng Zhou ◽  
Jianjun Bi ◽  
Qiang Feng ◽  
Zheng Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Primary Tumour ◽  
Cancer Center ◽  
Tumour Location ◽  
Life Threatening ◽  
Grade 3 ◽  
The Impact

Abstract Background The impact of primary tumour location on the prognosis of patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rarely discussed, and the evidence is still limited. Methods Patients with PM arising from CRC treated with CRS and HIPEC at the China National Cancer Center and Huanxing Cancer Hospital between June 2017 and June 2019 were systematically reviewed. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analysed. Results A total of 70 patients were divided into two groups according to either colonic or rectal origin (18 patients in the rectum group and 52 patients in the colon group). Patients with PM of a colonic origin were more likely to develop grade 3–4 postoperative complications after CRS+HIPEC (38.9% vs 19.2%, P = 0.094), but this difference was not statistically significant. Patients with colon cancer had a longer median overall survival (OS) than patients with rectal cancer (27.0 vs 15.0 months, P = 0.011). In the multivariate analysis, the independent prognostic factors of reduced OS were a rectal origin (HR 2.15, 95% CI 1.15–4.93, P = 0.035) and incomplete cytoreduction (HR 1.99, 95% CI 1.06–4.17, P = 0.047). Conclusion CRS is a complex and potentially life-threatening procedure, and we suggest that the indications for CRS+HIPEC in patients with PM of rectal origin be more restrictive and that clinicians approach these cases with caution.

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