Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8030-8030
Author(s):  
Steven R Hwang ◽  
Alexandra Higgins ◽  
Betsy LaPlant ◽  
Matthew J. Maurer ◽  
Stephen M. Ansell ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Patient Specific ◽  
Cox Regression Analysis

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.

scholarly journals 1196. Influence of antibiotic use on the effectiveness and safety of immune checkpoint inhibitors in Japan

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S620-S621
Author(s):  
Takuya Minamishima ◽  
Hirotake Hida ◽  
Kiyofumi Yamada
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Laboratory Data ◽  
Japanese Patients ◽  
Antibiotic Use ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Antibiotic Group

Abstract Background It has been reported that antibiotic use changes the gut microbiome and alters the outcome of treatment with immune checkpoint inhibitors (ICIs). However, in Asia, this has not been well studied, and there is insufficient evidence to support these reports. Methods In this study, we investigated the concurrent use of antibiotics and the administration of PD-1 inhibitors in Japanese patients, and examined the relationship between antibiotics and the clinical benefit or safety of PD-1 inhibitors. Results In total, 152 patients were analyzed: 62 patients received systemic antibiotics within 2 months before or 1 month after the first dose of PD-1 inhibitors (the antibiotic group); the remaining patients comprised the non-antibiotic group. There was a significantly higher proportion of patients under 65 years of age in the antibiotic group. Overall survival (OS) was not reached in the antibiotic and non-antibiotic groups, and there was no statistically significant difference between the two groups (HR = 1.48) (Figure 1). Progression-free survival (PFS) was 3.29 months in the antibiotic group and was significantly shorter than that in the non-antibiotic group (5.99 months, HR = 1.75) (Figure 2). Multivariate analysis by Cox regression analysis also showed that PFS was shorter in the antibiotic group (HR=1.63). As age may be a confounding factor, we performed a stratified analysis, a common method used to adjust for bias. The results of the stratified log-rank test after adjustment for age showed that the PFS was significantly shorter in the antibiotic group. There were no statistically significant differences between the two groups in the response rate, incidence of adverse events of Grade 3 or above, and laboratory data (Table 1). Figure 1 Figure 2 Table 1 Conclusion Our results suggest that the use of antibiotics may affect the anticancer treatment outcomes of Japanese patients who are administered PD-1. Disclosures All Authors: No reported disclosures

scholarly journals 191. The impact of antibiotic use on clinical outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S101-S101
Author(s):  
Maria Tsikala Vafea ◽  
Neel Belani ◽  
Kendra Vieira ◽  
Dimitrios Farmakiotis
Keyword(s):  
Cancer Patients ◽  
Clinical Outcomes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Experimental Models ◽  
The Impact

Abstract Background Observational studies and experimental models suggest that use of antibiotics close to the administration of immune checkpoint inhibitors (ICI) can negatively affect tumor response and patient survival. This observation may be attributed to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells. Methods We conducted a systematic search of PUBMED and EMBASE databases and references of articles retrieved. We included studies published between 1/1/17 and 2/1/20, which evaluated the association between antibiotic use and clinical outcomes in cancer patients treated with ICI. Primary endpoints were overall survival (OS), progression free survival (PFS), response rate (RR) and progressive disease (PD) rate. We performed a study-level random-effects meta-analysis with pooling of hazards ratios (HR) for OS, PFS, and odds ratios (OR) for RR and PD (PROSPERO ID: CRD42020166473). Results We included 41 studies with a total of 10,857 patients. The most common malignancies were lung cancer (59.7%), melanoma (23.1%), renal cell and urothelial carcinomas (8.1%). OS and PFS were shorter, RR lower, and PD higher in patients receiving antibiotics, both in univariate analyses and after adjustment for other confounders. Heterogeneity was significant for all outcomes, less so for adjusted OS and PFS (Table). To our knowledge, this is the largest meta-analysis on the association between antibiotic use and efficacy of ICI, and the only one to address RR and PD to-date. Association between antibiotics and clinical outcomes. Conclusion We demonstrated a significant association between antibiotic use and unfavorable clinical outcomes in patients with cancer receiving ICI. Such patients may be an important target group for antibiotic stewardship interventions. The high heterogeneity across all outcomes underscores the need for more detailed, patient-level studies with stratification by host, antibacterial and cancer treatment factors. Disclosures All Authors: No reported disclosures

scholarly journals Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study

2021 ◽  
Vol 7 ◽  
Author(s):  
Liyun Zheng ◽  
Shiji Fang ◽  
Fazong Wu ◽  
Weiqian Chen ◽  
Minjiang Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Factors Affecting ◽  
Pugh Class

Purpose: The study aims to retrospectively investigate the efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) (TACE+Sor) vs. TACE combined with sorafenib plus immune checkpoint inhibitors (TACE+Sor+ICIs) in treating intermediate and advanced TACE-refractory hepatocellular carcinoma (HCC).Materials and Methods: This study was approved by the ethics committee of Lisui Hospital, Zhejiang University, China. From January 2016 to June 2020, 51 eligible patients with intermediate or advanced TACE-refractory HCC received TACE+Sor (n = 29) or TACE+Sor+ICIs (n = 22). The differences in tumor response, adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Factors affecting PFS and OS were determined by Cox regression.Results: The disease control rate was higher in the TACE+Sor+ICIs group than in the TACE+Sor group (81.82 vs. 55.17%, P = 0.046). Compared with the TACE+Sor group, PFS and OS were prolonged in the TACE+Sor+ICIs group (median PFS: 16.26 vs. 7.30 months, P < 0.001; median OS: 23.3 vs. 13.8 months, P = 0.012). Multivariate analysis showed that BCLC stage, alpha-fetoprotein and treatment were independent factors of PFS; BCLC, Child-Pugh class, ablation after disease progression and treatment were independent predictive factors of OS. Four patients in the TACE+Sor+ICIs group and three patients in the TACE+Sor group suffered from dose reduction or interruption (18.18 vs. 10.34%, P = 0.421). The incidence of ICI-related AEs in the TACE+Sor+ICIs group was well-controlled.Conclusion: The therapeutic schedule of TACE+Sor+ICIs demonstrated efficacy and safety in intermediate and advanced TACE-refractory HCC.

Safety of immune checkpoint inhibitors in patients with preexisting autoimmune disorders.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14568-e14568
Author(s):  
Rohit Kumar ◽  
Abigail Sy Chan ◽  
Sudeepthi Bandikatla ◽  
Sarah Mudra ◽  
Smita Ranjan ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Cox Regression Analysis ◽  
Cancer Types ◽  
Baseline Characteristics ◽  
Grade 3

e14568 Background: In recent years, immune checkpoint inhibitors (ICIs) have been approved for a growing number of cancer types. Approximately 10-30% of cancer patients have a concomitant diagnosis of autoimmune disorders (AID). Activation of the immune system with ICIs poses a potential risk of AID worsening. The majority of the ICI clinical trials excluded these patients from the study. There is a paucity of data regarding the benefits and risks of ICIs in cancer patients with AIDs. The primary objectives of this study were to determine the incidence of immunotherapy related AID worsening and all immunotherapy related adverse events (irAEs). Secondary outcomes were time to AID worsening and survival difference. Methods: All adult patients (age ≥18 years) with solid malignancy who received ICIs between Jan 2016 to June 2019 were identified using the University of Louisville pharmacy database. Medical records were reviewed to include all the patients with preexisting AIDs. Descriptive statistics were used to determine the incidence of AID worsening and all irAEs. Baseline characteristics were compared between cancer patients with versus without AID worsening using Pearson chi2 and Student’s t-test, where appropriate. Multivariate Cox regression analysis was used to compared survival between the 2 groups. Results: A total of 40 patients with AIDs were identified during the study period. The cancer types were melanoma (57.5%), lung (15%), breast (5%), and others (22.5%). AIDs were rheumatological (52.5%), gastroenterological (12.5%), neurological (12.5%), dermatological (20%) and hematological (2.5%). The incidence of all irAEs was 60% (grade ≥3 in 20%) and AID worsening was 40% (grade ≥3 in 15%). Baseline characteristics of the 2 comparison groups are shown in table. The median time from ICI initiation to AID worsening was 94.5 (range 21-431) days. In multivariate Cox regression analysis, adjusted for demographics, cancer type, and stage, survival was similar for patients who had AID worsening versus those who did not (HR 0.30 (95%CI 0.06-1.40, p=0.128). Conclusions: In our single-institution study, cancer patients with preexisting AID do have an increased risk of irAEs with high-grade toxicities in 20% compared to historically reported 5% in the general cancer population; about 15% of patients reported grade ≥3 worsening of their AIDs. However, though the risk of irAEs is numerically higher in patients with AID, it may be acceptable to the patients if the potential benefits of ICIs outweigh the risks. Baseline demographics and clinical characteristics.[Table: see text]

Effect of antibiotic use on outcomes in patients with Hodgkin lymphoma treated with immune checkpoint inhibitors

2020 ◽  
pp. 1-5
Author(s):  
Steven R. Hwang ◽  
Alexandra Higgins ◽  
Natalia E. Castillo Almeida ◽  
Betsy LaPlant ◽  
Matthew J. Maurer ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Antibiotic Use

scholarly journals How to Choose a Survival Period? The Impact of Antibiotic Use on OS or PFS in NSCLC Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110334
Author(s):  
Hua Chen ◽  
Ke-dong Han ◽  
Zhi-jiang He ◽  
Yi-sheng Huang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Sensitivity Analyses ◽  
Clinical Activity ◽  
Nsclc Patients ◽  
The Impact

Background: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. Methods: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. Results: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [−60 days; 0 days] or [−30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [−60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. Conclusion: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.

The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Oncology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Oded Jacobi ◽  
Yosef Landman ◽  
Daniel Reinhorn ◽  
Oded Icht ◽  
Michal Sternschuss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Negative Relationship ◽  
Progression Free Survival ◽  
Significant Negative Correlation ◽  
Cox Proportional Hazards ◽  
Diabetic Patients

<b><i>Introduction:</i></b> Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. <b><i>Methods:</i></b> All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, <i>t</i> tests, and χ<sup>2</sup> tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. <b><i>Results:</i></b> Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], <i>p</i> = 0.011, and HR 1.5 [1.08–2.08], <i>p</i> = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], <i>p</i> = 0.79, and HR 1.29 [0.69–2.39], <i>p</i> = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. <b><i>Conclusion:</i></b> Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

scholarly journals Myocardial Metabolic Response Predicts Chemotherapy Curative Potential on Hodgkin Lymphoma: A Proof-of-Concept Study

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 971
Author(s):  
Cecilia Marini ◽  
Matteo Bauckneht ◽  
Anna Borra ◽  
Rita Lai ◽  
Maria Isabella Donegani ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cox Regression ◽  
Metabolic Response ◽  
Progression Free Survival ◽  
Disease Relapse ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Pet Ct ◽  
Genome Sharing

Genome sharing between cancer and normal tissues might imply a similar susceptibility to chemotherapy toxicity. The present study aimed to investigate whether curative potential of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is predicted by the metabolic response of normal tissues in patients with Hodgkin lymphoma (HL). METHODS: According to current guidelines, 86 patients with advanced-stage (IIB-IVB) HL, prospectively enrolled in the HD0607 trial (NCT00795613), underwent 18 F-fluorodeoyglucose PET/CT imaging at diagnosis and, at interim, after two ABVD courses, to decide regimen maintenance or its escalation. In both scans, myocardial FDG uptake was binarized according to its median value. Death and disease relapse were recorded to estimate progression-free survival (PFS) during a follow-up with median duration of 43.8 months (range 6.97–60). RESULTS: Four patients (4.6%) died, while six experienced disease relapse (7%). Complete switch-off of cancer lesions and cardiac lighting predicted a favorable outcome at Kaplan–Mayer analyses. The independent nature and additive predictive value of their risk prediction were confirmed by the multivariate Cox regression analysis. CONCLUSION: Susceptibility of HL lesions to chemotherapy is at least partially determined by factors featuring the host who developed it.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

2021 ◽  
pp. 1-11
Author(s):  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Melek Seren Aksun ◽  
Taha Koray Sahin ◽  
Gozde Kavgaci ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patients With Cancer ◽  
Early Progression ◽  
Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

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