Outcomes in patients with advanced non-small cell lung cancer (aNSCLC) and high PD-L1 expression treated with immune checkpoint inhibitor monotherapy: An FDA-pooled analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9606-9606
Author(s):  
Sujay Yogesh Shah ◽  
Jonathon Joseph Vallejo ◽  
Yutao Gong ◽  
Thomas D. Brown ◽  
Chenan Zhang ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Cell ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Cell Staining ◽  
Line Of Therapy ◽  
The Relationship

9606 Background: Higher PD-L1 score ≥ 50% predicts for greater benefit to immune checkpoint inhibitor (ICI) therapy in first line (1L) treatment of aNSCLC. It has recently been reported that PD-L1 score ≥ 90% predicts for even greater benefit to 1L ICI monotherapy (Aguilar et al., 2019). We examined pooled clinical trial databases to examine the relationship between high PD-L1 expression across multiple ICI monotherapies in 1L and second line (2L) treatment of aNSCLC. Methods: Data was pooled from trials (five 1L and five 2L) of ICI for the treatment of patients with aNSCLC. We defined PD-L1 score as the proportion of tumor cell stained by the assay (total of four assays identified) and included patients in the analysis with PD-L1 score ≥ 50%. Tumor-infiltrating immune cell staining was not considered. Progression-free survival (PFS) and overall survival (OS) by line of therapy for patients with PD-L1 score ≥ 90% and patients with PD-L1 score 50-89% was analyzed. Results: A total of 1320 patients treated with ICI monotherapy were identified, 873 in 1L and 447 in 2L. Median follow-up was 9.6 months in 2L patients and 13.3 months in 1L patients. Patients receiving 2L ICI therapy with PD-L1 score ≥ 90% (N = 208) had longer PFS and OS compared to patients with PD-L1 score 50-89% (N = 239), with mPFS 7.1 vs. 4.2 months (HR = 0.66 [95% CI: 0.52-0.83]) and mOS NR vs. 15.8 months (HR = 0.66 [95% CI: 0.49-0.89]). 1L ICI therapy analysis revealed similar trends, as patients with PD-L1 score ≥ 90% (N = 405) had longer PFS and OS compared to patients with a PD-L1 score 50-89% (N = 468), with mPFS 8.3 vs. 5.4 months (HR = 0.78 [95% CI: 0.66-0.92]) and mOS 22.9 vs. 16.4 months (HR = 0.74 [95% CI: 0.61-0.90]). Conclusions: This analysis showed the potential of an enhanced clinical benefit in patients with aNSCLC and PD-L1 score ≥90% across ICI monotherapies in both the 1L and 2L treatment setting. These data will be further analyzed in real world populations.

Thyroid immune-related adverse events following immune checkpoint inhibitor treatment

2021 ◽  
Author(s):  
Christopher A Muir ◽  
Roderick J Clifton-Bligh ◽  
Georgina V Long ◽  
Richard A Scolyer ◽  
Serigne N Lo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Thyroid Dysfunction ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Overt Hypothyroidism ◽  
Female Sex ◽  
Younger Age

Abstract Background Thyroid dysfunction occurs commonly following immune checkpoint inhibition. The etiology of thyroid immune-related adverse events (irAEs) remains unclear and clinical presentation can be variable. This study sought to define thyroid irAEs following immune checkpoint inhibitor (ICI) treatment and describe their clinical and biochemical associations. Methods We performed a retrospective cohort study of thyroid dysfunction in patients with melanoma undergoing CTLA-4 and/or PD-1 based ICI treatment from Nov 1, 2009 to Dec 31, 2019. Thyroid function was measured at baseline and at regular intervals following the start of ICI-treatment. Clinical and biochemical features were evaluated for associations with ICI-associated thyroid irAEs. The prevalence of thyroid autoantibodies and the effect of thyroid irAEs on survival were analysed. Results A total of 1246 patients were included with a median follow-up of 11.3 months. 518 (42%) patients developed an ICI-associated thyroid irAE. Subclinical thyrotoxicosis (n=234) was the most common thyroid irAE, followed by overt thyrotoxicosis (n=154), subclinical hypothyroidism (n=61), and overt hypothyroidism (n=39). Onset of overt thyrotoxicosis occurred a median of 5 weeks (IQR 2-8) after receipt of first dose of ICI. Combination immunotherapy was strongly associated with development of overt thyrotoxicosis (OR 10.8, 95% CI 4.51-25.6 vs. CTLA-4 monotherapy; p<0.001), as was female sex (OR 2.02, 95% CI 1.37-2.95; p<0.001) and younger age (OR 0.83 per 10-years, 95% CI 0.72-0.95; p=0.007). By comparison, median onset of overt hypothyroidism was 14 weeks (IQR 8-25). The frequency of overt hypothyroidism did not differ between different ICI-types. The strongest associations for hypothyroidism were higher baseline TSH (OR 2.33 per mIU/L, 95% CI 1.61-3.33; p<0.001) and female sex (OR 3.31, 95% CI 1.67-6.56; p=0.01). Overt thyrotoxicosis was associated with longer progression free survival (HR 0.68, 95% CI 0.49-0.94; p=0.02) and overall survival (HR 0.57, 95% CI 0.39-0.84; p=0.005). There was no association between hypothyroidism and cancer outcomes. Conclusions Thyroid irAEs are common and there are multiple distinct phenotypes. Different thyroid irAE subtypes have unique clinical and biochemical associations, suggesting potentially distinct etiologies for thyrotoxicosis and hypothyroidism arising in this context.

KMT2C as a positive predictor for treatment of immune checkpoint inhibitor and correlation with immune infiltrates in colorectal cancer (CRC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3538-3538
Author(s):  
Ling Zhang ◽  
Jianping Song ◽  
Yiting Wang ◽  
Yaoxu Chen
Keyword(s):  
Colorectal Cancer ◽  
Survival Data ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Cell ◽  
Checkpoint Inhibitor ◽  
Colon Adenocarcinoma ◽  
Treg Cells ◽  
Prognostic Effect

3538 Background: Lysine Methyltransferase 2C (KMT2C), a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family, possesses histone methylation activity and is involved in transcriptional co-activation. Present study has shown that KMT2C is positive correlated with better efficacy of Immune checkpoint inhibitor (ICI) in NSCLC. However, the role of KMT2C in treatment of ICI on colorectal cancer (CRC) is still unknown. Methods: NGS (Next Generation Sequencing) was performed on 1628 CRC patients. TMB of these patients were analyzed. A public accessible cohort (Samstein2018) with data from 130 CRC patients were used to investigate the correlation between KMT2C mutation and efficacy of ICI. WES and survival data of TCGA database (1099 CRC) was used to analyze prognostic effect of KMT2C mutation. Furthermore, CIBERSORT was used to analyze the tumor-infiltrating immune cells present in COAD（colon adenocarcinoma, 404 patients）from TCGA database. Results: Among 1628 CRC patient, 230(14.1%) had KMT2C mutation. TMB was positive correlated with KMT2C mutation (Mut vs. WT, 30.75 vs. 7.26 mut/Mb, p < 0.0001). The Samstein2018 cohort showed that KMT2C mutations (15.4%, 20/130) were significantly associated with better OS (Mut vs. WT, 11.5 vs. 7.5 month, HR = 0.29; 95% CI, 0.1-0.81; P = 0.012), and a higher TMB was also observed in KMT2C-Mut group (p = 1.98e-08). In TCGA, no association between KMT2C mutation and OS was observed (P = 0.23), suggesting that was not prognostic factor. Moreover, we analyzed the relationship between KMT2C mutation and immune cell infiltration through CRC TCGA database. The results showed, in COAD, KMT2C mutation was positively correlated with the abundance of CD8+ T cells (P = 0.0014), B cells (P = 0.014), M1 macrophages (P = 0.015), neutrophil (P = 0.0019) and NK cells (P = 0.043), and negatively correlated with Treg cells (p = 0.0063). Conclusions: KMT2C has an impact on the immune microenvironment and may be used as a potential positive predictor for treatment of ICI on CRC patients. The role of KMT2C in immunotherapy warrant further studies.

Venous thromboembolism events in patients with advanced cancer on immune checkpoint inhibitors

Immunotherapy ◽  
2021 ◽  
Author(s):  
Adi Kartolo ◽  
Cynthia Yeung ◽  
Gordon T Moffat ◽  
Lilian Hanna ◽  
Wilma Hopman ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Cancer Management ◽  
Thromboembolism Events

Aim: To evaluate the correlation between venous thromboembolism events (VTEs) and immune checkpoint inhibitor (ICI)-based regimens. Methods: This is a retrospective study of 403 patients with advanced cancer on ICI-based regimens. Results: We report 8% VTE incidence post-ICI initiation over a median of 11.1 months of follow-up. Compared with single-agent ICI, dual-ICI was significantly correlated with higher incidence of VTE (odds ratio [OR]: 4.196, 95% CI: 1.527–11.529, p = 0.005), but chemotherapy–immuno-oncology combination was not (OR: 1.374, 95% CI: 0.285–6.632, p = 0.693). Subsequent systemic therapy post-ICI was also independently associated with higher VTE incidence (OR: 2.599, 95% CI: 1.169–5.777, p = 0.019). Conclusion: Our findings suggest potential underreporting of VTE incidence in ICI clinical trials. As dual-ICI is becoming more prevalent in cancer management, clinicians should maintain vigilance regarding VTE in patients with advanced cancer on ICI-based regimens.

scholarly journals MLTI-03. FIRST-LINE STEREOTACTIC RADIOSURGERY COMBINED WITH SYSTEMIC TARGETED AND IMMUNE CHECKPOINT INHIBITOR THERAPY IN MELANOMA PATIENTS WITH NEWLY DIAGNOSED BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i14-i15
Author(s):  
Thatcher Heumann ◽  
Rebecca Ye ◽  
Peter Wu ◽  
Akram Habibi ◽  
Alexandra Sansosti ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Cumulative Incidence ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Newly Diagnosed ◽  
Comorbid Conditions ◽  
First Line

Abstract BACKGROUND: Of solid tumors, melanoma has the highest propensity for CNS spread with historic median survivals of 5–8 months following brain metastasis diagnosis. We evaluated the impact of systemic BRAF targeted and immune checkpoint inhibitor (ICI) therapies on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM) and assessed patient treatment burden associated with prolonged survival. METHODS: We retrospectively reviewed the demographics, disease characteristics, therapeutic regimens, overall survival, and first-year cumulative incidence of comorbid disease for patients with de novo MBM treated between 2013 and 2017 at a major melanoma referral center. RESULTS: Among 123 newly diagnosed MBM patients: 65% were male, 24% were 50 years old or less, 50% were BRAF mutated, 63% had multiple intracranial lesions at diagnosis. Locally, 73% received SRS as first-line treatment. Systemically, 73% received ICI, 46% received BRAF targeted therapy, and 12% received neither. With a median follow up of 11 months (mo), total cohort median OS was 13.2 mo. Median OS for first-line SRS combined with ICI and BRAF targeted therapy was 31.0 mo (47% 3-year OS), 17.5 mo (31% 3-year OS) with ICI monotherapy, and 6.1 mo (22% 3-yr OS) alone. SRS and BRAF targeted therapy were associated with improved OS. At one-year follow-up, comorbid conditions with the greatest cumulative incidence were fatigue, nausea, intracranial hemorrhage, deep vein thrombosis, major depressive disorder, and pneumonia. Patients averaged one inpatient visit every 4.5 mo (1 week average length of stay), and 2 advanced imaging studies (MR/CT/PET-CT) per month following MBM diagnosis. CONCLUSIONS: In one of the largest reported MBM series, survival has improved markedly for patients receiving first-line SRS combined with targeted and immunotherapies. Simultaneously, longer life expectancy comes with increasing incidences of comorbid conditions reflecting an evolving complexity of and need for coordination of care for patients with MBM.

scholarly journals Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation

2019 ◽  
Vol 79 (3) ◽  
pp. 332-338 ◽  
Author(s):  
Tawnie J Braaten ◽  
Julie R Brahmer ◽  
Patrick M Forde ◽  
Dung Le ◽  
Evan J Lipson ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Inflammatory Arthritis ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Tumour Response ◽  
Cox Proportional Hazards ◽  
Immunomodulatory Treatment ◽  
The Impact

ObjectiveWe sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies.MethodsWe conducted a prospective observational study of patients referred for IA associated with ICIs. Patients were recruited from June 2015 to December 2018. Information was obtained at the baseline visit, and follow-up visits occurred at varying intervals for up to 24 months from ICI cessation. Kaplan-Meier curves were developed to characterise IA persistence. Cox proportional hazards models were used to assess the influence of various factors on IA persistence. Logistic regression was used to evaluate the impact of IA treatment on tumour response.ResultsSixty patients were monitored with a median follow-up after ICI cessation of 9 months. A majority (53.3%) had active IA at their most recent follow-up. IA was less likely to improve in those with longer duration of ICI use, in those receiving combination ICI therapy, and in patients with multiple other immune-related adverse events. Tumour response did not appear to be impacted by immunosuppression. Although not statistically significant, persistent IA was correlated with a better tumour response (complete or partial response).ConclusionICI-induced IA can become a long-term disease necessitating management by rheumatology for immunomodulatory treatment. Importantly, the use of immunomodulatory treatment has not been shown to impact cancer outcomes in this study.

Efficacy of first-line immune checkpoint inhibitors in patients with sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC).

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 66-66
Author(s):  
Ziad Bakouny ◽  
Sarah Abou Alaiwi ◽  
Amin Nassar ◽  
John A. Steinharter ◽  
Xiao X. Wei ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Logistic Regressions

66 Background: Patients with mRCC with S/R components tend to have a poor prognosis with few therapeutic options available. Recent data suggest that immune checkpoint inhibitor (ICI)-based therapies may be especially effective for these patients. Our aim was to evaluate the efficacy of ICI-based therapies in patients with S/R mRCC. Methods: We retrospectively assessed objective response rate (ORR), progression free survival (PFS) & overall survival (OS) of patients with S/R mRCC treated at our institution with first-line ICI-based therapies and compared these to those of patients treated with first-line non-ICI-based therapies. Univariable and multivariable (adjusted for IMDC group) Cox and logistic regressions were performed. Results: 92 patients (70 S, 9 R, and 13 S&R) patients were included, of which 74 with a clear-cell component. For all patients (regardless of therapy), 74 (80.4%) patients experienced a PFS event (progression or death) and 52 (56.5%) died at 25.3 months (m) median follow-up. Overall median PFS was 5.3 m (95% CI= 3.4–7.2) and 24 m OS rate was 39.5% (27.4–51.7). Out of 78 patients in whom response was evaluable, ORR was 30.8% (20.4–41.2). Patients treated with ICI-based therapies had significantly better ORR, PFS, and OS on multivariable analysis (table). Conclusions: mRCC patients with S/R components have significantly better ORR, PFS, and OS with first-line ICI-based compared to non-ICI-based therapies. These data support the use of ICI-based therapies for patients with S/R mRCC. [Table: see text]

scholarly journals Analysis of Tumor Microenvironment Characteristics in Bladder Cancer: Implications for Immune Checkpoint Inhibitor Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingyu Chen ◽  
Haotian Chen ◽  
Dong He ◽  
Yaxin Cheng ◽  
Yuxing Zhu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Checkpoint Inhibitor ◽  
Clinical Prognosis

The tumor microenvironment (TME) plays a crucial role in cancer progression and recent evidence has clarified its clinical significance in predicting outcomes and efficacy. However, there are no studies on the systematic analysis of TME characteristics in bladder cancer. In this study, we comprehensively evaluated the TME invasion pattern of bladder cancer in 1,889 patients, defined three different TME phenotypes, and found that different subtypes were associated with the clinical prognosis and pathological characteristics of bladder cancer. We further explored the signaling pathways, cancer-immunity cycle, copy number, and somatic mutation differences among the different subtypes and used the principal component analysis algorithm to calculate the immune cell (IC) score, a tool for comprehensive evaluation of TME. Univariate and multivariate Cox regression analyses showed that ICscore is a reliable and independent prognostic biomarker. In addition, the use of anti-programmed death-ligand (PD-L1) treatment cohort, receiver operating characteristic (ROC) curve, Tumor Immune Dysfunction and Exclusion (TIDE), Subnetwork Mappings in Alignment of Pathways (SubMAP), and other algorithms confirmed that ICscore is a reliable prognostic biomarker for immune checkpoint inhibitor response. Patients with higher ICscore showed a significant therapeutic advantage in immunotherapy. In conclusion, this study improves our understanding of the characteristics of TME infiltration in bladder cancer and provides guidance for more effective personalized immunotherapy strategies.

scholarly journals Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns

2021 ◽  
Author(s):  
Ha Nguyen ◽  
Komal Shah ◽  
Steven G Waguespack ◽  
Mimi I Hu ◽  
Mouhammed Amir Habra ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Diagnostic Criteria ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
High Dose ◽  
Central Hypothyroidism ◽  
Central Adrenal Insufficiency ◽  
Mri Changes

Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI) related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted. IrH was defined as: (1) ACTH or TSH deficiency plus MRI changes or (2) ACTH and TSH deficiencies plus headache/fatigue in the absence of MRI findings. We found that of 83 patients followed for a median of 1.75 years (range 0.6-3), the proposed criteria used at initial evaluation accurately identified 61/62 (98%) irH cases. In the irH group (n=62), the most common presentation were headache (60%), fatigue (66%), central hypothyroidism (94%), central adrenal insufficiency (69%) and MRI changes (77%). Compared with non-Ipilimumab (Ipi) regimens, Ipi has a stronger association with irH occurrence (p=0.004) and a shorter time to irH development (p<0.01). Thyroid, gonadal and adrenal axis recovery occurred in 24%, 58% and 0% patients, respectively. High dose steroids (HDS) or ICI discontinuation were not associated with hormonal recovery. In the non-irH group (n=19), one patient had isolated central hypothyroidism and 6 had isolated central adrenal insufficiency. All remained on hormone therapy at last follow up. We propose a strict definition of irH that identifies the vast majority of patients. HDS and ICI discontinuation is not always beneficial. Long term follow up to assess recovery is needed.

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