Correlation of pathogenic POLE mutations with clinical benefit to immune checkpoint inhibitor therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3008-3008
Author(s):  
Benjamin Garmezy ◽  
Jinesh S. Gheeya ◽  
Kyaw Zin Thein ◽  
Patrick Glen Pilie ◽  
Wanlin Wang ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Cancer Center ◽  
Chi Square ◽  
Dna Polymerase Epsilon ◽  
Number Variation ◽  
Md Anderson ◽  
Chi Square Analysis

3008 Background: Mutations in DNA polymerase epsilon ( POLE) may induce DNA replication errors, increasing neoantigen load and potentially enhancing clinical benefit to immune checkpoint inhibitors (ICI). We present a clinicopathologic analysis of patients (pts) with advanced cancers harboring POLE mutations and their response to ICI therapy at MD Anderson Cancer Center. Methods: We used targeted exome sequencing via CLIA-certified next generation sequencing assays to identify pts with POLE-aberrant tumors and their co-occurring mutations. The pathogenicity of each POLE mutation was annotated utilizing InterVar and ClinVar databases. Chi-square analysis was performed. Results: Tumors from 12,947 pts were analyzed and 448 (3.5%) pts had a mutation or copy number variation in POLE (3.5%), comparable to the TCGA PanCancer Atlas (4.0%). Clinical data were available for 293 pts; the most common cancers were colorectal (14.7%), non-small cell lung (13.7%), cholangiocarcinoma (13.3%) and melanoma (10.2%). There were 267 unique co-mutations, including KRAS (23.0%), ARID1A (21.5%), BRCA2 (18.7%), ATM (18.4%), CDKN2A (17.5%), BRAF (15.3%), EGFR (15.3%), ATRX (12.6%), CREBBP (11.7%), APC (11.3%), ATR (11.0%), BRCA1 (11.0%) and CDK12 (10.4%). POLE variants were annotated in all pts: pathogenic/likely pathogenic (n = 34, 11.6%), benign/likely benign (61, 20.8%), and variant of unknown significance (198, 67.6%). 104 (35.8%) of 293 pts with POLE mutations received PD-1/L1 inhibitors as monotherapy or in combination. 93 (88.4%) of 104 pts were evaluable for response: Radiological CR 4.3% (n = 4), PR 26.9% (n = 25), SD 22.6% (n = 21), PD 46.2% (n = 43), for a clinical benefit rate (CR + PR + SD) of 53.8%. Pathogenic status of POLE mutation was associated with clinical benefit to PD-1/L1 inhibitors (p = 0.04). TMB (p = 0.44), PD-L1 (p = 0.11), and MSI (p = 0.66) status were not associated with pathogenic status. MSI-H status was not over-represented in pts with ICI clinical benefit (p = 0.36). Conclusions: Pathogenic POLE mutations were associated with clinical benefit to ICI therapy. Further studies are warranted to validate POLE mutations as a predictive biomarker. Multiple co-occurring DNA damage response mutations were found, which may contribute to ICI clinical benefit.

Maintenance immunosuppressive therapy with resumption of immune checkpoint inhibitor treatment to reduce recurrence of immune-mediated colitis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2642-2642
Author(s):  
Hamzah Abu-Sbeih ◽  
Fangwen Zou ◽  
Barbara Dutra ◽  
Mehmet Altan ◽  
Jennifer Leigh McQuade ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immunosuppressive Therapy ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Cancer Center ◽  
Adequate Treatment ◽  
Univariate Logistic Regression Analysis ◽  
Immune Mediated ◽  
Md Anderson ◽  
Current Guidelines

2642 Background: Immune-mediated colitis (IMC) may limit immune checkpoint inhibitors (ICI) treatment. Current guidelines recommend consideration of resuming ICI when IMC symptoms subside to ≤ grade 1. We aimed to investigate the effect of maintenance immunosuppressive therapy (IST) on the outcome of IMC in patients who resume ICI therapy. Methods: We retrospectively studied patients who resumed ICI therapy after adequate treatment of IMC from March 2015 to June 2020 at MD Anderson Cancer Center. Relevant demographic, oncologic, and ICI data were collected and analyzed. Univariate logistic regression analysis was conducted to assess risk factors of IMC recurrence. Results: We included 102 patients with a median age of 61 years. 66% were males and 97% were Caucasians. 48 patients (47%) received IST maintenance in conjunction with ICI resumption and 54 patients did not. Symptoms of IMC recurred in 28 patients, 8 (17%) in the concurrent IST group and 20 (37%) in the other group. Compared to no concurrent IST group, patients on concurrent IST were more likely to have received combined ICI regimen (60% vs 41%, p = 0.003) and more initial ICI doses (9 vs 5 doses, p = 0.030). Concurrent IST group had significantly longer ICI treatment duration on resumption (72 vs 62 days, p = 0.023), more ICI resumed doses (5 vs 4 doses, p = 0.038), and lower IMC recurrence (17% vs 37%, p = 0.027). Patient who received more IST doses, both therapeutic and prophylactic, had lower rate of IMC recurrence (OR 0.72, p = 0.012; table). IST maintenance treatment (OR 0.34, p = 0.024) was associated with lower IMC recurrence rate after ICI resumption. Vedolizumab was the predominant IST used. Overall survival was comparable among the two groups (p = 0.934). Conclusions: Concurrent IST treatment with ICI resumption after IMC was associated with significantly lower IMC recurrence and more extended ICI treatment while reserving similar overall survival to patients without IST maintenance therapy. Future prospective randomized trial of concurrent IST is still merited for further clarification.[Table: see text]

scholarly journals Clinical Characteristics and Outcomes of Oral Mucositis Associated With Immune Checkpoint Inhibitors in Patients With Cancer

2021 ◽  
Author(s):  
Jake S. Jacob ◽  
Barbara E. Dutra ◽  
Victor Garcia-Rodriguez ◽  
Kavea Panneerselvam ◽  
Fiyinfoluwa O. Abraham ◽  
...  
Keyword(s):  
Oral Mucositis ◽  
Immune Checkpoint ◽  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Cancer Center ◽  
Symptom Duration ◽  
University Of Texas ◽  
Md Anderson

Background: Immune checkpoint inhibitor (ICI) therapy predisposes patients to immune-related adverse events (irAEs). Data are limited regarding the incidence, management, and outcomes of one such irAE: mucositis. In this study, we evaluated the clinical characteristics, disease course, treatment, and outcomes of ICI-mediated mucositis. Methods: This was a retrospective, single-center study of patients who received ICI therapy and developed oral mucositis at The University of Texas MD Anderson Cancer Center from January 2009 to September 2019. Inclusion criteria included age ≥18 years, a diagnosis of oral mucositis and/or stomatitis based on ICD-9 and ICD-10 codes, and therapy using CTLA-4 or PD-1/L1 inhibitors alone or combined with other agents. Results: We identified 152 patients with a mean age of 60 years, 51% of whom were men. Of the sample patients, 73% had stage IV cancer, with melanoma the most common (28%). Median time from ICI initiation to mucositis was 91 days. The most common clinical presentation of mucositis was odynophagia and/or oral pain (89%), 91% developed CTCAE grade 1–2 mucositis, and 78% received anti–PD-1/L1 monotherapy. Compared with anti–PD-1/L1–based therapy, anti–CTLA-4–based therapy was more frequently associated with earlier onset of mucositis (73 vs 96 days; P=.077) and a lower rate of symptom resolution (76% vs 92%; P=.029); 24% of patients required immunosuppressive therapy, which was associated with longer symptom duration (84 vs 34 days; P=.002) and higher mucositis recurrence rate (61% vs 32%; P=.006). ICI interruption was associated with worse survival (P=.037). Mucositis recurrence, immunosuppressant use, and presence of other irAEs did not affect survival. Conclusions: For ICI-mediated mucositis, a diagnosis of exclusion has not been well recognized and is understudied. Although the clinical symptoms of mucositis are mostly mild, approximately 25% of patients require immunosuppression. Mucositis recurrence can occur in approximately 39% patients. Our results showed that ICI interruption compromises overall survival.

scholarly journals Clinicopathologic Features, Treatment Response, and Outcomes of Immune Checkpoint Inhibitor–Related Esophagitis

2021 ◽  
Vol 19 (8) ◽  
pp. 896-904
Author(s):  
Kavea Panneerselvam ◽  
Rajan N. Amin ◽  
Dongguang Wei ◽  
Dongfeng Tan ◽  
Phillip J. Lum ◽  
...  
Keyword(s):  
Treatment Response ◽  
Immune Checkpoint ◽  
Clinical Presentation ◽  
Checkpoint Inhibitors ◽  
Gastrointestinal Toxicity ◽  
Categorical Variables ◽  
Cancer Center ◽  
Continuous Variables ◽  
Chi Square ◽  
Upper Gastrointestinal

Background: Although immune checkpoint inhibitors (ICIs) have provided practice-changing outcomes in treating many cancers, ICI-related gastrointestinal toxicity can limit their use. Upper gastrointestinal toxicity is not common nor as well described as lower gastrointestinal toxicity. We aimed to characterize the clinical presentation, endoscopic and histologic features, treatment response, and outcomes of ICI-related esophagitis. Methods: We retrospectively studied patients at The University of Texas MD Anderson Cancer Center in whom esophagitis developed after receiving ICIs from June 2011 through January 2020. We included patients with endoscopic evidence of esophagitis and excluded those with other obvious causes of esophagitis. A chi-square test was used to assess associations between categorical variables. The Mann-Whitney U test was used to compare differences between continuous variables. Results: Of 657 consecutive patients who underwent esophagogastroduodenoscopy (EGD) during or within 6 months of completing ICI-based therapy, 21 (3%) had esophagitis deemed to be from ICIs. Of these patients, 1 (5%) received an inhibitor of CTLA-4 alone, 15 (71%) received anti–PD-1 or PD-L1 monotherapy, and 5 (24%) received a combination of these. Median time from ICI initiation to onset of esophagitis was 4 months. Upon evaluation with EGD, only 3 patients (14%) had isolated esophageal involvement; 18 (86%) had concurrent involvement of the stomach, duodenum, or both. Most patients (67%) were treated with proton pump inhibitors, and 4 (19%) received steroids (prednisone or budesonide). The mortality rate was 38% (median follow-up, 15 months). Conclusions: Esophagitis associated with ICI use is rare. The diagnosis is one of exclusion because its clinical presentation appears similar to that of inflammation resulting from other causes. It often occurs in conjunction with other upper gastrointestinal toxicity. Symptoms are mild and respond well to nonimmunosuppressive treatment, with few severe complications.

657 Interleukin-6 receptor blockade for management of immune checkpoint inhibitor related adverse events in patients with melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A694-A694
Author(s):  
Chantal Saberian ◽  
Faisal Fa’ak ◽  
Jean Tayar ◽  
Maryam Buni ◽  
Sang Kim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Median Time ◽  
Interleukin 6 ◽  
Immune Checkpoint ◽  
Activity Index ◽  
Critical Role ◽  
Cancer Center ◽  
Interleukin 6 Receptor ◽  
Md Anderson

BackgroundManagement of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients.MethodsWe searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed.ResultsMedian age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%).ConclusionsOur data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

Impact of medical mistrust (MM) on perceptions of tumor genomic profiling (TGP) among African American (AA) cancer patients: Application of perceptual mapping (PM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22527-e22527
Author(s):  
Michael J. Hall ◽  
Paul D'Avanzo ◽  
Yana Chertock ◽  
Jesse A Brajuha ◽  
Sarah Bauerle Bass
Keyword(s):  
Cancer Patients ◽  
Test Performance ◽  
Information Needs ◽  
University Hospital ◽  
Urban Site ◽  
Cancer Center ◽  
Medical Mistrust ◽  
Chi Square ◽  
Perceptual Mapping ◽  
Chi Square Analysis

e22527 Background: TGP is widely used to identify targetable mutations for precision cancer treatment and clinical trials. Many patients have poor understanding of TGP and are unaware of possible secondary hereditary risks. Lack of clarity regarding the relevance of informed consent and genetic counseling further magnify risks for patients. AA patients have lower genetic knowledge and health literacy and higher MM than Caucasian patients, making them especially vulnerable in the clinical setting. Perceptions of TGP in AA cancer patients have not been well-characterized. Methods: 120 AA pts from 1 suburban and 1 urban site (Fox Chase Cancer Center[FCCC] and Temple University Hospital[TUH]) were surveyed. A k-means cluster analysis using a modified MM scale was conducted; chi-square analysis assessed demographic differences. Perceptual mapping (PM)/multidimensional scaling and vector modeling was used to create 3-dimensional maps to study how TGP barriers/facilitators differed by MM group and how message strategies for communicating about TGP may also differ. Results: Data from 112 analyzable patients from FCCC (55%) and TUH (45%) were parsed into less MM (MM-L, n = 42, 37.5%) and more MM (MM-H, n = 70, 72.5%) clusters. MM-L and MM-H clusters were demographically indistinct with no significant associations by sex (p = 0.49), education (p = 0.3), income (p = 0.65), or location (p = 0.43); only age was significant (older = higher MM, p = 0.006). Patients in the MM-H cluster reported higher concerns about TGP, including cost (p < 0.001), insurance discrimination (p < 0.001), privacy breaches (p = 0.001), test performance/accuracy (p = 0.001), secondary gain by providers (p < 0.001) and provider ability to explain results (p = 0.04). Perceptual mapping identified both shared and contrasting barriers between MM clusters (Table). Conclusions: More than 2/3 of AA patients comprised a MM-H cluster. Communication strategies should focus on concerns about family and how to discuss TGP with an oncologist. PM can identify distinct and shared information needs of vulnerable populations undergoing TGP. [Table: see text]

scholarly journals 236 Predictors of ICI renal toxicity: a pathological approach

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A252-A252
Author(s):  
Ala Abudayyeh ◽  
Liye Suo ◽  
Heather Lin ◽  
Omar Mamlouk ◽  
Cassian Yee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Toxicity ◽  
Checkpoint Inhibitors ◽  
Interstitial Fibrosis ◽  
Transplant Rejection ◽  
Categorical Variables ◽  
Rank Test ◽  
Cancer Center ◽  
Renal Response ◽  
Md Anderson

BackgroundInflammatory response in unintended tissues and organs associated with the use of immune checkpoint inhibitors also known as immune related adverse events (irAEs) is a management challenge, and renal irAEs are associated with increased patient morbidity and mortality. The most common renal toxicity is acute interstitial nephritis (AIN), characterized by infiltration of renal tissue with immune cells, and may be analogous to kidney transplant rejection. Using both clinical variables and tissue findings we evaluated a large cohort of ICI cases to determine predictors of renal response and overall survival.MethodsWe retrospectively reviewed all patients treated with ICI (August 2007 to August 2020) at MD Anderson Cancer Center. A total of 38 patients with biopsy confirmed AIN and available tissue were identified. All slides were reviewed by two board certified renal pathologists and the severity of inflammation and chronicity was graded using transplant rejection BANFF criteria. Patients were categorized as renal responders if creatinine improved or returned to baseline after treatment and non-responders if it did not. Fisher’s exact tests for categorical variables and t-test/ANOVA or the counterparts of the non-parametric approaches (Wilcoxon rank-sum or Kruskal-Wallis) for continuous variables were used to compare patient‘s characteristics between groups. The distribution of overall survival (OS) was estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups.ResultsBased on the detailed pathological findings, patients with increased interstitial fibrosis were less likely to have renal response with treatment compared to patients with less fibrosis, (p < 0.05). Inflammation, tubulitis, number of eosinophils and neutrophils had no impact on renal response. Patients with response within 3 months of AKI treatment had a superior OS in comparison to patients who responded late (12-month OS rate: 77% vs 27%, p < 0.05). Notably, patients who received concurrent ICI and achieved renal response within 3 months had the best OS while those who did not receive concurrent ICI nor achieved renal response had worst OS (12-month OS rate: 100% (renal response and concurrent ICI) vs 72% ( renal response with no concurrent ICI), vs 27% ( no renal response and nonconcurrent ICI) (p < 0.05).ConclusionsThis is the first analysis of ICI induced nephritis where a detailed pathological and clinical evaluation was performed to predict renal response. Our findings highlight the importance of early diagnosis and treatment of ICI-AIN while continuing concurrent ICI therapy.Ethics ApprovalThis retrospective study was approved by the institutional review board at The University of Texas MD Anderson Cancer Center, and the procedures followed were in accordance with the principles of the Declaration of Helsinki.

CCND1 amplification profiling identifies a subtype of melanoma associated with poor survival and an immunosuppressive tumor microenvironment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21552-e21552
Author(s):  
Yu Chen ◽  
Liu Jun ◽  
Jing Lin ◽  
Xuefeng Wang ◽  
Xiao-bin Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Lipid Metabolism ◽  
Immune Checkpoint ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Antiangiogenic Agents ◽  
Ccnd1 Amplification ◽  
Melanoma Patients

e21552 Background: Melanoma is generally regarded as an immunogenic type of tumor that will respond to immune checkpoint therapy. However, melanoma tumors with CCND1 amplification respond poorly to checkpoint therapy. Further understanding of how CCND1 amplification modifies the effect of checkpoint therapy is necessary to design future clinical trials. Methods: We used the data from the Geneplus Institute (n = 302), The Cancer Genome Atlas (TCGA) (n = 367),and the Memorial Sloan Kettering Cancer Center (MSKCC) (n = 350) to identify the incidence of CCND1 amplification and the relationship between CCND1 amplification and survival in melanoma patients and explored molecular mechanisms. Results: The frequency of CCND1 amplification co-occurring with BRAF V600, NRAS, NF1, and KIT mutations was low in these three cohorts. Data from TCGA did not show a statistically significant correlation between CCND1 amplification levels and prognosis of melanoma patients irrespective of immune checkpoint inhibitors (ICIs). In contrast, we found opposite results using the MSKCC cohort where CCND1 amplification was an unfavorable prognostic factor for melanoma patients. This was especially true for patients received ICIs who were harboring a high tumor mutation burden (TMB). The TCGA data showed that CCND1 amplification were related to a higher proportion of immunosuppressive cells (Treg cells and M2 macrophages) and a lower proportion of immunity boosting cells (follicular helper T-cells, naive B-cells, CD8+ T-cells). Furthermore, GSEA analysis from the TCGA database suggests that the signaling pathways such as oxidative phosphorylation, reactive oxygen species, adipogenesis, fatty acid metabolism, DNA repair, and myc targets were differentially enriched in melanoma tumors with CCND1 amplification. Finally, we found that angiogenesis related molecules (HIF1A, VEGFA, VEGFR1, FGF2, FGFR1, FGFR4, HGF, PDGFA, PDGFRA, ANGPT1, and ANGPT2) were remarkable decreased in a CCND1 High Amplification group from the TCGA database. Conclusions: Melanoma with CCND1 amplificationis an independent genomic subtype associated with a poor prognosis, an immunosuppressive TME, activated oxidative and lipid metabolism, and down-regulated angiogenesis. Taken together, avoiding ICIs and antiangiogenic agents, while employing CDK4/6 inhibitors alone or in combination with ICIs, targeting oxidative and lipid metabolism pathway may be effective and promising therapeutic strategies for melanoma patients harboring CCND1 amplification.

Expansion of pharmacist clinical services to optimize the management of immune checkpoint inhibitor toxicities

2019 ◽  
Vol 25 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Catherine E Renna ◽  
Elizabeth N Dow ◽  
Jason J Bergsbaken ◽  
Ticiana A Leal
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Management Program ◽  
Cancer Center ◽  
Caregiver Education

Introduction The development of immune checkpoint inhibitors has revolutionized cancer treatment and is now a part of the treatment paradigm for several malignancies. Although immune checkpoint inhibitors are generally well tolerated, treatment is associated with immune-related adverse events, some serious and potentially life threatening. Early identification and prompt appropriate management of immune-related adverse events are crucial to prevent morbidity and mortality. The complexity and severity of immune-related adverse events require interdisciplinary collaboration to optimize care. Patient and caregiver education and continued communication between patients and members of the oncology care team are vital for timely recognition and successful management of immune-related adverse events. The objective of this program is to provide a proof of concept; a pharmacist-led immune checkpoint inhibitor management program will increase early recognition and management of immune-related adverse events through patient and caregiver education and proactively assessing patients for toxicities. Methods At the University of Wisconsin Carbone Cancer Center, we developed and implemented a pharmacist-driven program, referred to as the immune checkpoint inhibitor program, which aimed to ensure patient and caregiver education and continuous monitoring of immune-related adverse events. This program utilized pharmacist–patient encounters to improve patient and caregiver education and follow-up monitoring. The design and implementation are detailed. Pharmacist interventions and patient outcomes were evaluated. Results At interim analysis, 47 patients were enrolled in the program and pharmacists completed 34 interventions on 26 patients. Pharmacists are well positioned to educate patients and caregivers on immune checkpoint inhibitor therapy and provide proactive monitoring to detect immune-related adverse events. We hypothesize that the interventions made by pharmacist may lead to earlier recognition and treatment of immune-related adverse events.

scholarly journals Circulating Tumor Cell PD-L1 Expression as Biomarker for Therapeutic Efficacy of Immune Checkpoint Inhibition in NSCLC

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 809 ◽  
Author(s):  
Kloten ◽  
Lampignano ◽  
Krahn ◽  
Schlange
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Advanced Nsclc ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Immune Checkpoint Blockade ◽  
Tissue Samples ◽  
Programmed Death ◽  
Nsclc Patients

Over the last decade, the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced non-small cell lung cancer (NSCLC) patients. PD-L1 tumor expression, along with tumor mutational burden, is currently being explored as a predictive biomarker for responses to immune checkpoint inhibitors (ICIs). However, lung cancer patients may have insufficient tumor tissue samples and the high bleeding risk often prevents additional biopsies and, as a consequence, immunohistological evaluation of PD-L1 expression. In addition, PD-L1 shows a dynamic expression profile and can be influenced by intratumoral heterogeneity as well as the immune cell infiltrate in the tumor and its microenvironment, influencing the response rate to PD-1/PD-L1 axis ICIs. Therefore, to identify subgroups of patients with advanced NSCLC that will most likely benefit from ICI therapies, molecular characterization of PD-L1 expression in circulating tumor cells (CTCs) might be supportive. In this review, we highlight the use of CTCs as a complementary diagnostic tool for PD-L1 expression analysis in advanced NSCLC patients. In addition, we examine technical issues of PD-L1 measurement in tissue as well as in CTCs.

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