Correlation of immunity-related adverse events with survival and response to anti-PD-1 treatment in patients with metastatic melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15164-e15164
Author(s):  
Bozena Cybulska-Stopa ◽  
Iwona Lugowska ◽  
Marcin Zietek ◽  
Anna Dawidowska ◽  
Anna Malgorzata Czarnecka ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Cox Model ◽  
Univariate Analysis ◽  
Response To Therapy ◽  
Real World Data ◽  
Kaplan Meier ◽  
Programmed Cell Death 1 ◽  
Melanoma Patients ◽  
Number Of Cycles

e15164 Background: Immunotherapy has become a standard treatment option for metastatic melanoma patients, and the use of anti-programmed cell death-1 monoclonal antibodies (anti-PD-1) has significantly improved the outcomes of this group of patients. Immune related adverse events (irAEs) during anti-PD-1 treatment may present a significant problem. However, irAEs' relationship with overall survival although suggested in single studies was not confirmed in real world data. Methods: Consecutive patients starting treatment between March 2016 and April 2019 with fist line anti-PD-1 (nivolumab or pembrolizumab) for unresectable or metastatic melanoma in 6 comprehensive cancer centers in Poland were enrolled in the study. Baseline patients characteristics and irAEs development during treatment were evaluated to identify predictors of progression-free (PFS) and overall (OS) survival in Cox model. PFS and OS were assessed using Kaplan–Meier method. Results: Overall, 410 patients were included in the present analysis and 107 patients experienced irAEs. Response rate (RR) and disease control rate (DCR) were 36% (148 pts) and 65% (267 pts) respectively. Median PFS and OS were 7.6 (2.8–21.6) and 21.6 (6.7–38.2) months, respectively. In univariate analysis normal LDH level, no brain metastases, ECOG 0 or 1, ≤ 2 number of metastases locations were positive prognostic factors for both OS and PFS. At the same time irAEs occurrence was correlated with longer PFS, OS, RR and DCR (all p < 0.001); moreover high LDH level correlated with irAEs (p = 0.027) development. There was no correlation between irAEs and the number of cycles of anti-PD-1 patients received. Conclusions: Our study showed an association between irAEs and longer survival on anti-PD1 therapy in patients with advanced or metastatic melanoma. An association with irAEs and response to therapy has also been demonstrated.

Anaemia: A risk factor for death and adverse outcomes following surgery for acute lower limb ischaemia

Vascular ◽  
2021 ◽  
pp. 170853812110261
Author(s):  
Daniel Perren ◽  
Lauren Shelmerdine ◽  
Luke Boylan ◽  
Craig Nesbitt ◽  
James Prentis ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cox Model ◽  
Univariate Analysis ◽  
Adverse Outcomes ◽  
Limb Ischaemia ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Acute Limb Ischaemia ◽  
Impact On Survival ◽  
Poor Outcomes

Introduction Acute limb ischaemia (ALI) forms a significant part of the vascular surgery workload and carries with it high rates of morbidity and mortality. Anaemia is also common amongst vascular surgical patients and has been linked with poor outcomes in some subgroups. We aimed to assess the frequency of anaemia in patients with ALI and its impact on survival and complications following revascularisation to help direct future efforts to optimise outcomes in this patient group. Methods A retrospective analysis of prospectively collected departmental data on patients undergoing surgical intervention for ALI between 2014 and 2018 was performed. Anaemia was defined as a pre-operative haemoglobin (Hb) of <120 g/L for women and <130 g/L for men. The primary outcome was overall survival, assessed with the Kaplan–Meier estimator, with application of Cox proportional hazard modelling to adjust for confounding covariates. Results There were 158 patients who underwent treatment for ALI: 89 (56.3%) of these were non-anaemic with a mean Hb of 146 (SD = 18.4), and 69 (43.7%) were anaemic with a mean Hb of 106 (SD = 13.4). Anaemic patients had a significantly higher risk of death than their non-anaemic counterparts on univariate analysis (HR = 2.11, 95% CIs, 1.28–3.5, p = 0.0036). There was ongoing divergence in survival up to around 6 months between anaemic and non-anaemic groups. Under the Cox model, anaemia was similarly significant as a predictor of death (HR = 2.15, 95% CIs, 1.17–3.95, p = 0.013), accounting for recorded comorbidities, medication use and blood transfusion. Conclusions Anaemia is a significant and independent risk factor for death following revascularisation for ALI and can be potentially be modified. Vascular surgical centres should ensure they have robust pathways in place to identify and consider treating anaemia. There is scope for further work to assess how to best optimise a patient’s levels of circulating haemoglobin.

scholarly journals Comparison of Efficacy in Patients with Metastatic Melanoma Treated with Ipilimumab and Nivolumab Who Did or Did Not Discontinue Treatment Due to Immune-Related Adverse Events: A Real-World Data Study

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5550
Author(s):  
Morten Fink ◽  
Anders Schwartz Vittrup ◽  
Lars Bastholt ◽  
Inge Marie Svane ◽  
Marco Donia ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Real World ◽  
Negative Impact ◽  
Cox Proportional Hazards Model ◽  
Induction Phase ◽  
Discontinue Treatment ◽  
Real World Data ◽  
World Data ◽  
Significant Difference

Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30–40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma.

Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 556-556 ◽  
Author(s):  
Takeru Wakatsuki ◽  
Eiji Shinozaki ◽  
Mitsukuni Suenaga ◽  
Izuma Nakayama ◽  
Tomohiro Matsushima ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adverse Events ◽  
Univariate Analysis ◽  
Rank Test ◽  
Multikinase Inhibitor ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Almost All ◽  
Therapy Target

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14035-e14035
Author(s):  
Daniele Fanale ◽  
Lorena Incorvaia ◽  
Gaetana Rinaldi ◽  
Lidia Terruso ◽  
Giuseppe Badalamenti ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Primary Tumor ◽  
Primary Melanoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Rank Test ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes ◽  
First Time

e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasma PD-1 levels were analyzed in 28 patients with metastatic melanoma using a specific ELISA assay. The characterization of TILs in tumor tissue was performed by immunohistochemistry. Statistical analysis was assessed using t-Student and ANOVA tests. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Results: 16 out of 28 patients showed the presence of TILs in primary tumor, 10 of which brisk and 6 nonbrisk. The plasma PD-1 levels were analyzed in relation to the presence/absence of TILs (p = 0.022), brisk TILs versus nonbrisk/absent TILs (p = 0.014), and brisk vs nonbrisk vs absent TILs (p = 0.032). In particular, low plasma PD-1 levels have been shown to be associated with brisk TILs in primary melanoma, intermediate values with nonbrisk TILs, and high expression with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant association between the plasma PD-1 expression levels and overall survival (OS) depending on the absence or presence of TILs (brisk/nonbrisk), however the median survival of patients having brisk TILs was five months higher than other 2 groups of patients with absent and nonbrisk TILs, respectively. Conclusions: This work highlights, for the first time, the potential ability of using the plasma PD-1 levels to predict prognosis also in patients with metastatic melanoma at diagnosis for which it is not possible to identify the primary tumor.

A clinical prognosis model for Asian advanced melanoma patients receiving immunotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14081-e14081
Author(s):  
Xuan Wang ◽  
Xieqiao Yan ◽  
Zhihong Chi ◽  
Lu Si ◽  
Xinan Sheng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Metastases ◽  
Tumor Size ◽  
Cox Model ◽  
Univariate Analysis ◽  
Advanced Melanoma ◽  
Braf Mutations ◽  
Clinical Prognosis ◽  
C Statistic ◽  
Melanoma Patients

e14081 Background: Immunotherapy PD-1 inhibitor therapy shows relative lower efficacy in Asia especially in acral and mucosal subtypes. The identification of predictive factors of immunotherapy remains a crucial but unmet clinical need. The objective of this study was to evaluate advanced melanoma patients treated with anti-PD-1 in order to identify risk factors for PFS, OS and develop a prognostic scoring system for immunotherapy. Methods: Patients with unresectable melanoma treated with PD-1 inhibitor enrolled on trials between 2015 and 2017 at Peking University Cancer Center were included. A nomogram to predict survival was developed based on a multivariable Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan–Meier curve and calibration plots. Results: The discovery cohort comprised 133 patients with unresectable melanoma. 38.3% acral and 21.8% mucosal melanomas were included, 26.3% with liver metastases, 31.6% with an elevated serum LDH, 20.3% harbored BRAF mutations. The median PFS was 4.8 months, based on the Cox model, four factors were selected for the nomogram and assigned specific scores: tumor metastases number≥3, 1; tumor size≥80 mm,1; LDH level, 1 (higher limit of normal range); liver metastases,1. The model achieved relatively good discrimination and calibration, with a C-statistic of 0⋅804 (Table). BRAF mutations were associated with shorter PFS in univariate analysis but not in multivariate analysis. Subtypes were also not related to PFS in this cohort. The median OS was 22.8 months. Univariate analysis identified eight factors were associated with significantly worse OS among 21 factors ( BRAF and subtype included, which not found as risk factors). Based on the Cox model, five factors were selected for the nomogram and assigned specific scores: ECOG > 1, 0.6; Hemoglobin < 120g/ml,0.6; tumor size≥80 mm,1.4; LDH level, 0.5; liver metastases, 1. C-statistic was 0⋅85, with extremely strong predictability (Table). The overall survival rate for patients with a higher score was significantly worse than lower cohort (Score: < 0.6 vs. 1-2 vs. 2-4.1; OS: not reached vs. not reached vs. 8.3m; P < 0⋅001). Conclusions: The nomogram facilitates personalized assessment of prognosis for Asian patients with advanced melanoma with PD-1 inhibitor. [Table: see text]

The impact of BRAF mutation status on clinical outcomes with single-agent PD-1 inhibitor versus combination ipilimumab/nivolumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10024-10024
Author(s):  
Vincent The-Luc Ma ◽  
Stephanie Daignault ◽  
Jessica Waninger ◽  
Leslie Anne Fecher ◽  
Michael Green ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Retrospective Analysis ◽  
Braf Mutation ◽  
Univariate Analysis ◽  
Single Agent ◽  
Mutation Status ◽  
Melanoma Patients ◽  
The Impact ◽  
Braf Mutant ◽  
Braf V600 Mutation

10024 Background: Nearly half of all metastatic melanoma patients possess the BRAF V600 mutation. Several therapies are approved for BRAF mutant metastatic melanoma, but it is unclear if there is a differential outcome to various immunotherapy regimens. Our aim was to better assess if BRAF mutation status has any impact on survival to combination ipilimumab/nivolumab (I/N) versus single-agent PD-1 inhibitor (PD-1i). Methods: We performed a single center, retrospective analysis on a cohort of patients diagnosed with metastatic or unresectable melanoma from 2012 to 2019 at the University of Michigan who were treated with standard I/N or PD-1i (nivolumab or pembrolizumab). A univariate analysis of progression free survival (PFS) and overall survival (OS) was stratified by treatment type and BRAF mutation status. A multivariate Cox regression of survival was used to compare the effects of the treatment groups adjusted by BRAF status, age, gender, pre-treatment LDH level, prior treatment status, and brain metastases status. Results: 323 patients were identified. 132 had BRAF V600 mutation and 191 had BRAF wildtype (WT) status. 138 patients received I/N and 185 patients received PD-1i. In our univariate analysis, there was no difference in PFS [HR: 0.72, 95% CI, 0.46 – 1.13] or OS [HR: 0.78, 0.44 – 1.38] with I/N versus PD-1i in the BRAF mutant cohort, but there was improved PFS [HR: 0.55, 0.35 – 0.88) and OS [HR: 0.52, 0.28 – 0.95] with I/N compared to PD-1i in the BRAF WT group. In the multivariate analysis, the BRAF WT group continued to show PFS benefit with I/N compared to PD-1i [HR: 0.57, 95% CI, 0.35 – 0.95], but the OS benefit no longer achieved statistical significance [HR: 0.54, 0.28 – 1.03]. Conclusions: Our study results were discordant with the observation in the landmark CheckMate 067 trial, which noted improved PFS and OS with I/N compared to nivolumab alone in the BRAF mutant group and no difference in the BRAF WT group. In our real-world retrospective analysis, I/N over PD-1i should be considered as initial immunotherapy for metastatic melanoma patients regardless of BRAF mutation status, but even more favorably in BRAF WT.

Insurance status and survival of multiple myeloma (MM) patients.

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. LBA107-LBA107 ◽  
Author(s):  
Kamal Chamoun ◽  
Marcos J.G. De Lima ◽  
Paolo Fabrizio Caimi ◽  
Pingfu Fu ◽  
Shufen Cao ◽  
...  
Keyword(s):  
Cox Model ◽  
Private Insurance ◽  
Univariate Analysis ◽  
Insurance Status ◽  
Median Income ◽  
Academic Institutions ◽  
Regional Income ◽  
Kaplan Meier ◽  
The Usa ◽  
Income Data

LBA107 Background: MM is often treated with oral antineoplastic medications (OAM). OAM prices have been rapidly escalating and there are well-described issues with affordability (Shih et al. JCO 2017). We therefore hypothesized that insurance status influences MM patients (pts) survival and interrogated the National Cancer Database (NCDB) to test this hypothesis. Methods: NCDB houses data on 70% of cancer pts in the USA. Data from 117,926 MM pts diagnosed between year 2005 and 2014 was analyzed. Primary outcome was overall survival (OS) which was analyzed using Kaplan-Meier method and Cox model. Results: Median age at diagnosis was 67 years (19-90); 55% were males. 57% of pts lived in areas where the median income was < $46k/year (individual income data was not available); Primary insurance was Medicare (52%), private insurance (35%) or Medicaid (5%), and 3% were uninsured. 40% were treated in academic institutions. Median follow up was 30 months (0-145). By univariate analysis, better OS was observed in pts with primary MM, lower Charlson Comorbidity Index (CCI), treatment in academic institutions, higher median regional income, or private insurance ( p<0.0001 for all). Median age of pts on Medicare, private insurance, Medicaid, or those without insurance was 74, 57, 58, and 57 years, respectively. When restricting the analysis to pts ≥ 65 years old, pts with private insurance had longer OS compared to Medicare pts (p<0.0001). The table shows the results of MV analysis. Conclusions: Insurance type and regional income are associated with MM survival. This may be related to affordability of OAM and merits further investigation. [Table: see text]

scholarly journals Immunotherapy for Metastatic Melanoma with Right Atrial Involvement in a Patient with Rheumatoid Arthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Zachary Benson ◽  
Sarah Gordon ◽  
Patricia Nicolato ◽  
Andrew Poklepovic
Keyword(s):  
Rheumatoid Arthritis ◽  
Heart Failure ◽  
Surgical Treatment ◽  
Autoimmune Disease ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Response To Therapy ◽  
Right Atrial ◽  
Durable Response ◽  
Life Threatening

Prognosis for metastatic melanoma has improved significantly with the use of immune checkpoint inhibitors. Given improvements in survival, aggressive surgical treatment may be considered in patients with life-threatening complications from their disease that would not otherwise be considered in advanced disease. Patients with preexisting autoimmune diseases or prior immune-related adverse events from therapy are largely excluded from clinical trials. Concerns exist that immunotherapy in these patients could worsen autoimmune disease or increase the risk of developing additional immune-related adverse events on therapy. We present a case of a patient with rheumatoid arthritis that presented with obstructive heart failure secondary to melanoma that had metastasized to the right atrium. After aggressive surgical resection to stabilize him from his life-threatening heart failure, he was treated with ipilimumab, which was stopped due to an immune-related adverse event. He was then started on pembrolizumab and had a durable response to therapy. Aggressive surgical treatment should be considered in patients with a cancer that may respond to immunotherapy. Furthermore, some patients with preexisting autoimmune disease may be safely treated with checkpoint inhibition therapy, and patients with a severe immune toxicity from one class may successfully be treated with an alternate class.

Delta-radiomics for prediction of pseudoprogression in malignant melanoma treated with immune checkpoint inhibition.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9575-9575 ◽  
Author(s):  
Lucas Basler ◽  
Hubert Gabrys ◽  
Sabrina A. Hogan ◽  
Marta Bogowicz ◽  
Diem Vuong ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Prediction Models ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Response Rates ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Melanoma Patients

9575 Background: Distinguishing progressive disease (PD) from pseudoprogression (PP) in patients treated with immune-checkpoint inhibition (ICI) is challenging and usually requires confirmation follow-up imaging or invasive diagnostic techniques. This project aimed to identify predictive radiomic signatures for PP from CT imaging. Methods: The response to ICI of 105 metastatic melanoma patients with 645 metastases was retrospectively correlated with radiomic signatures (172 total features). All metastatic lesions were delineated at 3 time points: prior to ICI (t0), at 3 (t1) and 6 months (t2). Response was defined individually for each metastasis using RECIST 1.1, comparing baseline t0 to t2. Three prediction models for PP were built: CT radiomics at t0 and t1, as well as the relative difference between both t0 and t1 (delta-radiomics). Results: Median follow-up was 18 months and 2-year OS and PFS were 72% and 25%, respectively. Median OS: not reached, median PFS: 6 months. Response per lesion at t1: 13% complete remission (CR), 19% partial remission (PR), 52% stable disease (SD) and 16% PD. At t2: 16% CR, 31% PR, 38% SD and 15% PD. 106 progressive lesions were identified at t1, of which, 26 changed to SD, 1 to CR and 3 to PR at t2, resulting in 30 PPs (4.7%). Metastasis location significantly influenced response rates but was not associated with PP (p = 0.4). Lung metastases had significantly higher response rates than soft tissue (p < 0.001), liver (p < 0.001) and bone metastases (p = 0.008). Univariate analysis followed by removal of correlated features revealed no significant radiomic features associated with PP at t0. One independent feature was identified at t1 (AUC 0.74), while delta-radiomics was the best performing approach, identifying four independent features (AUC 0.72 to 0.81). A final multivariate delta radiomics logistic regression model was generated and internally validated, achieving an AUC of 0.81 (± 0.11, 10-fold cross-validation). Conclusions: Metastasis location significantly influenced response rates and CT-based delta-radiomics is a promising biomarker for early differentiation between pseudoprogression and true progression in metastatic melanoma patients treated with ICI.

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