Prognostic relevance of neutrophil to lymphocyte ratio (NLR) before anti-PD1 therapy in metastatic melanoma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21045-e21045
Author(s):  
Daniel Vilarim Araujo ◽  
Rafael Vanin de Moraes ◽  
Victor Aurelio Ramos Sousa ◽  
Mauro Daniel Spina Donadio ◽  
Aline Fusco Fares ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Metastatic Melanoma ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Melanoma Patients

e21045 Background: Biomarkers to select the patients most likely to benefit from checkpoint inhibitors are urged. NLR is a simple way of measuring systemic inflammation and is an independent predictor of survival before Anti-CTLA4 therapy. We hypothesized if NLR is also a predictor of survival before Anti-PD1 therapy. Methods: We performed a retrospective review of the medical records of all consecutive metastatic melanoma patients who received Nivolumab treatment from January/2014 – February/2017, including 53 patients prospectively collected from an Expanded Access Program. Of 86 patients, 83 patients were included for demographic and efficacy analysis, and 74 had information about baseline pre-treatment NLR. We analyzed NLR as a continuous variable and categorised ≥ 5 vs. < 5. Kaplan-Meier method was used for survival analysis. Long-rank test compared categories and Cox proportional hazards regression model was used to assess the prognostic significance of baseline NLR in univariate and multivariable analysis. Results: Median PFS for the entire population was 6,407 months (3,28 – 9,52) and median OS was not reached (NR) with a median FU of 10,74 months. The median NLR ratio was 3,11 (0,87 – 19). 18 patients (24,3%) had a ≥ 5 NLR vs. 56 (75,7%) < 5. Median PFS for NLR ≥ 5 was: 2,3 (1,75 – 2,84) vs. 12,02 (5,11 – 18,93) for < 5 (HR = 3,11; IC95% 1,52 – 6,27; p = 0,001). Median OS ≥ 5: 3,05 (2,06 – 4,04) vs. NR for < 5 (HR = 5,88; IC95% 2,60 – 13,29; p = 0,001). NLR categorised remained statistically significant in multivariate analysis for PFS and NLR as a continuous variable remained statistically significant for both PFS and OS in multivariate analysis (Table 1). Conclusions: Baseline NLR is a rapid, simple, and cost-free predictor of survival before Anti-PD1 therapy. These results should be validated in a larger cohort of patients. [Table: see text]

Plasma proteomic analyses and treatment predictive biomarker candidates in melanoma patients receiving immune checkpoint blockade or targeted therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9574-9574 ◽  
Author(s):  
Hanna Eriksson ◽  
Haris Babacic ◽  
Janne Lehtio ◽  
Maria Pernemalm
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Mapk Pathway ◽  
Predictive Biomarkers ◽  
Cox Proportional Hazards ◽  
Protein Levels ◽  
Treatment Type ◽  
Melanoma Patients

9574 Background: The introduction of immune checkpoint inhibitors (ICIs) or therapies targeting the MAPK-pathway (MAPKis) has significantly improved clinical outcomes in metastatic melanoma patients. Still, a large proportion of the patients become resistant to therapy and there is a need for treatment predictive biomarkers. The aim of this study was to analyze the treatment predictive biomarkers based on the plasma proteome of patients with metastatic melanoma treated with ICIs or MAPKis. Methods: We analyzed serial plasma samples from 48 patients with metastatic melanoma collected; 24 patients were treated with ICIs and with MAPKis, respcetively. A non-biased, high-resolution isoelectric focusing of peptides-liquid chromatography-mass spectrometry (HiRIEFLC-MS/MS)-based method, and with proximity ligation assays (PEA) targeting 92 immuno-oncology-related proteins were used.We analyzed the change in protein levels during treatment with a paired t-test, and their association with progression free survival (PFS) with Cox proportional hazards models. Results: HiRIEFLC-MS/MS detected 1,835 proteins.We detected statistically-significant log2-fold-changes in 109 protein levels out of 1,160 proteins tested (not corrected for multiple testing). PDCD-1 had the highest log2-fold change (FC = 1.27) after treatment (p = 0.02). After stratifying for treatment type, PDCD-1 levels increased in patients treated with ICIs (FC = 2.13, p= 0.0008), but not in MAPKis-treated patients. PEA analyses confirmed this observation. The PEA panel showed association between 44 proteins and shorter PFS (pcoefficient <0.05, pLRT<0.05, qLRT<0.05), among them: LGALS1, CSF1, VEGFA, CASP8, CCL2, TNFSF14, ANGPT2, IL10, IL6, and ADGRG1. Of these, increase in plasma levels during treatment of LGALS1, CCL2 and ADGRG1 were associated with longer PFS. HiRIEF LC-MS/MS detected 69 proteins associated with PFS (pcoefficient< 0.05, pLRT< 0.05, qLRT < 0.05). Conclusions: By using HiRIEFLC-MS/MS, we could detect putative treatment predictive proteins in plasma from patients with metastatic melanoma treated with ICIs or MAPKis. Our findings require further validation.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

scholarly journals Disparity in outcomes of melanoma adjuvant immunotherapy by demographic profile

2020 ◽  
Vol 7 (2) ◽  
pp. MMT43
Author(s):  
Alexandra Ikeguchi ◽  
Michael Machiorlatti ◽  
Sara K Vesely
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Demographic Factors ◽  
Cox Proportional Hazards ◽  
Adjuvant Immunotherapy ◽  
Node Positive ◽  
Melanoma Patients ◽  
The Impact

Background: Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors. Materials & methods: We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan–Meier method and Cox proportional hazards models. Results: All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy. Conclusion: Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.

Pre-treatment neutrophil to lymphocyte ratio (NLR) association with curative intent metastasectomy (MSX) in metastatic renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16051-e16051
Author(s):  
Aline Fusco Fares ◽  
Daniel Vilarim Araujo ◽  
Eliza Dalsasso Ricardo ◽  
Marcelo Corassa ◽  
Maria Nirvana Cruz Formiga ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Regression Tree ◽  
Positive Association ◽  
Cox Proportional Hazards ◽  
Curative Intent ◽  
Risk Of Death ◽  
Metastatic Rcc

e16051 Background: NLR is a marker of inflammation and when elevated is associated with poor outcome in many tumors, including RCC. Hereby we evaluate the association of NLR with the likelihood of curative intent MSX. Methods: We retrospectively studied 846 patients diagnosed with metastatic RCC between 2007 and 2016. 116 patients fulfilled inclusion criteria: previous nephrectomy, no sarcomatoid features and available tumor specimens from metastatic site. Regression tree for censored data method was used to find the best NLR cut-off value. NLR was examined baseline – prior to MSX or targeted therapy. Chi-square test was used to evaluate associations between variables. We estimated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards regression models were fitted to evaluate the prognostic significance of NLR in univariable and multivariable analysis. Results: The median OS for the whole cohort was 45 months (95% CI, 27.6 to 62.4 months), and the median follow-up was 78.2 months. The best cut-off NLR value was 4.07. Higher NLR was associated with shorter OS when compared to the lower NLR cohort (11.5 months vs 68.3 months HR = 0.26, 95% CI: 0.15 – 0.97, p ≤ 0.0001, respectively). Univariate analysis revealed that bone metastasis and poor IMDC criteria were associated with worse OS and that MSX and lower NLR were associated with better OS. On multivariate analysis MSX, lower NLR and favourable/intermediate group on IMDC criteria were associated with a decreased risk of death (HR = 0.41, 95% CI 0.19-0.85, p = 0.018 and HR = 0.45, 95% CI 0.22-0.90, p = 0.025, HR = 0.35, 95% CI 0.16-0.79, p = 0.012, respectively). We found a positive association of lower NLR and curative intent MSX (p = 0.002). Conclusions: NLR is a prognostic marker in metastatic RCC and a ratio ≤ 4,07 is associated with a higher likelihood of curative intent MSX.

del(17p13.1) in Chronic Lymphocytic Leukemia Confers Poor Prognosis Even at Low Percentage Involvement and Increases Proportionately with Increase in Clonal Involvement.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2073-2073 ◽  
Author(s):  
Leslie A. Andritsos ◽  
Jeffrey Jones ◽  
Gerard Lozanski ◽  
Thomas S. Lin ◽  
Kristie A. Blum ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Proportional Hazards ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Time To Progression

Abstract Background: The del(17p13.1) abnormality has been shown to have great prognostic significance in chronic lymphocytic leukemia (CLL), predicting a shorter time to progression and decreased overall survival when compared with other chromosomal abnormalities and a normal karyotype. We sought to assess the significance of low percentage del 17p in untreated patients with CLL. Patients and Methods: Patients with B-cell CLL who had received no prior therapy were eligible for evaluation. At the time of initial visit, baseline variables were collected including patient demographics, Rai stage, peripheral blood immunophenotyping, routine cytogenetic evaluation and FISH analysis (described below), and beta-2-microglobulin. Patients were followed for time to progressing (defined as need for first therapy) and overall survival. Cytogenetic and FISH analyses were performed according to standard laboratory methods. Probes for FISH were D12Z1 (12 centromere), TP53 del(17p13.1), del(11q22.3) and D13S319 del(13q14), (all from Abbott Molecular) and were used according to manufacturer directions. For each sample, 200 nuclei were analyzed per probe, 100 nuclei by each of two analysts. The association between percentage del(17p13.1) and time to progression, defined as time from FISH to initiation of treatment, was explored using Cox proportional hazards regression. For purposes of analysis, percentage del(17p13.1) was alternately considered as both a continuous and dichotomous variable (various cut points at 5% increments). Results: From August 2001 to February 2006, 54 untreated patients with CLL were found on initial evaluation to have del(17p13.1) ≥ 5% of nuclei analyzed. The median age was 61 (range 45–90), with 36 males and 18 females. At the time of initial FISH analysis, 14 patients had Rai stage 0 disease, 22 had Rai stage 1 disease, 10 had Rai stage 2 disease, and 8 had Rai stages 3 or 4 disease. 50 patients were evalualuable for time to progression and overall survival. Considered as a continuous variable, del(17p13.1) percent positive was associated with a significantly increased hazard for shorter time to progression. For each 10% increase in del(17p13.1) percentage, there was a 20% increase in the hazard for shorter time to disease progression [HR 1.20, 95%CI(1.05, 1.37), p=0.007]. Using alternative cutpoints for a positive test, del(17p13.1) percentage was associated with an increased hazard for TTP at all percentages greater than 10, an association that became statistically significant at 25%. Conclusion: del(17p13.1) in CLL predicts for shorter time to first treatment even at lower percentages, with the hazard ratio increasing with increasing percentage. Further study in a larger patient sample is warranted to determine whether del17p should be considered significant even at lower percentages not currently defined as “positive.” Figure Figure

scholarly journals Expression and Prognostic Significance of NPC1L1 in Colorectal Cancer: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Ryuk Jun Kwon ◽  
Soo Min Son ◽  
Eun Ju Park ◽  
Sang Yeoup Lee ◽  
Jungin Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Gene Expression Omnibus ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Chi Square ◽  
Independent Prognostic Marker ◽  
Niemann Pick

Abstract Background: Colorectal cancer (CRC) is a malignant tumor of the large intestine. Studies have shown that the development and prognosis of CRC are associated with altered lipid metabolism. Niemann-Pick C1-Like 1 (NPC1L1), the target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, the role of altered NPC1L1 expression in the development and prognosis of CRC has not yet been determined.Methods: Datasets of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) database. To compare the expression of NPC1L1 in normal and CRC tissues, datasets obtained from the GDAC platform were used. To support these results, we also analyzed other datasets from the Gene Expression Omnibus (GEO) database. Student’s t-test and chi-square test were used for the analyses. The log-rank test and multivariate Cox proportional hazards regression analysis were performed to determine whether NPC1L1 is a significant factor affecting the prognosis of CRC.Results: The mRNA expression of NPC1L1 was found to be upregulated in CRC, and was significantly associated with the N- and pathological stages, but not with the histological type, age, and sex. Moreover, an increase in NPC1L1 expression in CRC was associated with poorer survival, based on the Kaplan–Meier and multivariate regression analyses.Conclusions: High expression of NPC1L1 is associated with CRC development, pathological stage, and prognosis. The present study suggests that NPC1L1 represents a potential independent prognostic marker for CRC.

Impact of age at diagnosis on survival of hormone-refractory prostate cancer (HRPC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16050-e16050
Author(s):  
M. R. Humphreys ◽  
C. Ma ◽  
S. S. Sridhar
Keyword(s):  
Multivariate Analysis ◽  
Bone Metastasis ◽  
Proportional Hazards ◽  
Survival Curve ◽  
Performance Status ◽  
Retrospective Chart Review ◽  
Cox Proportional Hazards ◽  
Age At Diagnosis ◽  
Rank Test ◽  
Androgen Ablation

e16050 Background: Conflicting data exist for age as a determinant of overall survival (OS) in pts with HRPC. We hypothesize that young (<55) HRPC pts represent a more aggressive biological phenotype and therefore have a decreased OS. Methods: A retrospective chart review was conducted on 334 consective HRPC pts treated between 1995–2005. Summary statistics for demographic and clinical factors were generated, and Kaplan-Meier (KM) OS curves were created. Bivariate Cox Proportional-Hazards regression was used to test the association of age at diagnosis while adjusting for a covariate, with significant covariates entered into multivariate models. Results: Overall median survivals in the age stratified categories (<55, ≥55–65, ≥65–75, ≥75) were 5.5, 6.9, 7.9, and 4.3 yrs, with 5 yr survivals 51.9%, 67.4%, 67.0%, and 34.9%, respectively. KM curves showed divergence with an overall significant log-rank test (p < 0.0001). Compared to pts ≥65–75, the hazard ratios (HR) for HRPC pts <55 and ≥75 were 1.40 (95% CI 0.90–2.60) and 2.52 (95% CI 1.67–3.82), respectively. However, following multivariate analysis HRs for HRPC pts <55 and ≥75 were 1.60 (95% CI 0.98–2.62) and 1.25 (95% CI 0.71–2.20). Pts <55 and ≥75 presented with advanced stage at diagnosis and progressed to bone metastasis earlier. Pts ≥75 had decreased performance status, more comorbidities, higher PSA at diagnosis, shorter duration of hormone sensitive disease, and were less likely to receive chemotherapy than pts <75. The percentage of rapid PSA doubling times was highest in the <55 cohort. In multivariate analysis with age as a categorical variate, ECOG 3–4 (HR 2.65), time from diagnosis to both HRPC (HR 0.78) and bone metastasis (HR 0.80), and duration of response to androgen ablation (HR 0.86) remained highly predictive. Conclusions: Age at diagnosis influences OS in HRPC with a bimodal survival curve. Pts <55 and ≥75 present with more aggressive disease, translating into reduced median and 5 yr survivals. Other covariates, especially ECOG status, likely account for the decreased OS in the ≥75 cohort. Conversely, pts <55 had an adjusted HR of 1.60 (p = 0.06). Our study supports a growing body evidence that suggests a poor prognosis in younger men; correlating these differences at the molecular level could lead to better targeted therapies. No significant financial relationships to disclose.

Neutrophil/lymphocyte ratio (NLR) as a prognostic factor in biliary tract cancer (BTC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4130-4130
Author(s):  
Mairead Geraldine McNamara ◽  
Arnoud J. Templeton ◽  
Manjula Maganti ◽  
Thomas Walter ◽  
Anne M Horgan ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Inflammatory Marker ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Neutrophil Lymphocyte Ratio ◽  
Tract Cancer

4130 Background: BTCs include intrahepatic (IHC), hilar, distal bile duct (DBD), and gallbladder carcinoma (GBC). Risk factors include conditions associated with chronic inflammation. NLR, an inflammatory marker, is prognostic in several cancers but has not been reviewed in large BTC series, hilar or GBC. Methods: Baseline demographics and NLR at diagnosis were evaluated in 864 patients (pts) with BTC from 01/87 - 12/12 treated at Princess Margaret Cancer Center. Their prognostic significance for overall survival (OS) was determined using a Cox proportional hazards model. Results: High NLR ≥3.0 was associated with poor survival using univariable analysis as was stage/site of primary (P<0.05), age >65yrs, lymphocytes ≤1.6 (P<0.01), neutrophils ≥5.0, platelets ≥280, hemoglobin (Hb) < 110 g/L (P<0.001). Median OS in pts with NLR<3.0 was 21.6 mo, 12.0 mo with NLR ≥3.0 (P<0.001). NLR retained its significance as a prognostic marker on multivariable analysis (Table), along with GBC (P<0.05), age>65yrs, DBD primary (P<0.01), stage and Hb <110g/L (P<0.001). NLR was prognostic for OS on multivariable analysis for hilar: overall (Table) and advanced grp (n=102) (HR 1.68, 95%CI 1.07-2.64, P<0.05) and in advanced DBD (n=102) (HR 1.63, 95%CI 1.03-2.57,P<0.05). On subgrp analysis, NLR was prognostic for OS in advanced BTC (ABTC) (n=538) (P<0.01) but not in surgical grp. NLR did not predict RECIST response to first line palliative chemotherapy in ABTC. Conclusions: Baseline NLR is prognostic in BTC, specifically ABTC and hilar subgrp, suggesting the importance of systemic inflammation influencing outcome in pts with ABTC, thus providing a simple inexpensive prognostic biomarker while also possibly identifying pts that may benefit from antiinflammatory mediation. NLR was not predictive for response in BTC. [Table: see text]

Analysis of the GERCOR index in KRAS Exon2 WT patients with mCRC treated with salvage-line cetuximab-based chemotherapy: HGCSG0901.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 781-781
Author(s):  
Ayumu Hosokawa ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Kazuteru Hatanaka ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Impact ◽  
Significant Difference

781 Background: The GERCOR index (GI) based on performance status and serum LDH was reported to be useful to predict survival for patients with previously untreated mCRC. However, in the salvage setting, the validity of the GI has not been reported in patients treated with cetuximab (Cmab)-based chemotherapy. Methods: 269 patients with mCRC treated with Cmab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS Exon2 wild type patients who were refractory to or intolerant of 5-FU / irinotecan/ oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival (OS) were performed using patient characteristics. Survival analyses were performed with the Kaplan-Meier method, log-rank test and the Cox proportional hazards model. The analysis was also designed to determine whether the GERCOR index could be extended to progression-free survival (PFS). Results: All data were available for prognostic categorization in 132 patients. Median OS and PFS were 9.8 and 4.3 months. The distribution and median OS / PFS for GI were as follows: low risk (L)(n = 28; 17.9/3.8 months), intermediate risk (I)(n = 52; 12.2/5.0 months), and high risk (H)(n = 52; 7.5/4.1 months). For OS, there was significant difference between L and H (p < 0.001) and between I and H (p < 0.001), but not between L and I (p = 0.076). For PFS, there was significant difference between I and H (p = 0.017), but not between L and I (p = 0.407), and between L and H (p = 0.222). In the Cox multivariate analysis, GI showed an independent prognostic impact (L vs. I ; HR 2.195, p=0.003 / L vs. H ; HR 4.028, p<0.001), but not predictive impact (L vs. I ; HR 0.987, p=0.958 / L vs. H ; HR 1.314, p=0.268). Conclusions: In this analysis, GI might be a prognostic factor in salvage treatment with Cmab-based chemotherapy.

Risk of non-infectious uveitis or myasthenia gravis in patients on checkpoint inhibitors in a large healthcare claims database

2020 ◽  
pp. bjophthalmol-2020-317060 ◽  
Author(s):  
Tian Xia ◽  
Alexander J Brucker ◽  
Brendan McGeehan ◽  
Brian L VanderBeek
Keyword(s):  
Multivariate Analysis ◽  
Myasthenia Gravis ◽  
Index Date ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
History Of ◽  
Infectious Uveitis

AimTo determine if checkpoint inhibitors (CPIs) confer an increased risk of non-infectious uveitis or myasthenia gravis (MG) compared to patients on non-checkpoint inhibitor (N-CPI) chemotherapy.MethodsA retrospective cohort study was performed comparing patients in a large commercial and Medicare advantage database exposed to CPI compared to N-CPI. All patients who initiated a CPI (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab and durvalumab) were eligible. Date of earliest CPI in the exposure group and N-CPI chemotherapy in the comparator group was considered the index date. Exclusion occurred in both cohorts for any history of uveitis or MG diagnosis and having <1 year in the insurance plan prior to the index date, and <6 months in plan following the index date. Every exposed patient was matched up to 1:10 based on demographics and index year to patients on N-CPI chemotherapy. Multivariate Cox proportional hazards regression modelling was performed.ResultsFor evaluation of incidence of non-infectious uveitis, 26 (0.3%) of 8678 patients on CPI and 123 (0.2%) of 76 153 N-CPI comparators were found to have non-infectious uveitis. After multivariate analysis, CPIs showed an increased hazard for uveitis compared to N-CPI (HR=2.09; 95% CI 1.36 to 3.22, p=0.001). For the MG analysis, 11 (0.1%) of 9210 patients developed MG in the CPI group and 36 (0.04%) of 80 620 comparators. The CPI cohort had a higher hazard of developing MG (HR=2.60; 95% CI 1.34 to 5.07, p=0.005) compared to controls in multivariate analysis.ConclusionsExposure to CPI confers a higher risk for non-infectious uveitis and MG compared to N-CPI chemotherapy.

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