bluuebunny/crossref_metadata_2025_split huggingface dataset:
IBI310 monotherapy or in combination with sintilimab in patients with advanced melanoma: An open-label phase Ia/1b study.
Authors: Lian Bin , Cui Chuanliang , Si Lu , Sheng Xinan , Chi Zhihong , Mao Lili , Tang Bixia , Wang Xuan , Yan Xieqiao , Li Siming , Bai Xue , Zhou Li , Guo Jun , Zhou Hui , Xia Huan 
Published: May 2020

e15111 Background: IBI310 is a humanized IgG1 monoclonal antibody against CTLA-4. The study evaluates the safety and tolerability of IBI310 alone or in combination with sintilimab, a PD-1 inhibitor, in patients (pts) with advanced melanoma. Methods: This phase 1a/1b study contained three parts: Part A, Part B and Part C (NCT03545971). In Part A, pts with advanced melanoma were treated in an accelerated titration design with 0.3 mg/kg IBI310 (Q3W, IV), or a 3+3 escalation design with 1, 2 or 3 mg/kg IBI310 (Q3W, IV), up to 3 cycles. In Part B, pts with advanced melanoma were administrated in a 3+3 escalation design with 1, 2 or 3 mg/kg IBI310 (Q3W, IV) plus sintilimab (200 mg, Q3W, IV) for 4 cycles, followed by sintilimab maintenance therapy (200 mg, Q3W, IV). Part C was dose expansion of the combination therapy. The primary objective was to determine dose-limiting toxicity (DLT) of IBI310 monotherapy and the second was efficacy of the combination therapy. Tumor evaluation was based on RECIST 1.1. Results: As of Nov 12, 2019, 10 pts were enrolled in Part A (median age 55.5), 6 were mucosal melanoma, 3 were acral melanoma and 1 was non-chronic sun damaged (NCSD) melanoma; 17 pts were enrolled in Part B and C (median age 47.0), only 1 (5.9%) was chronic sun damaged (CSD), and 16 (94.1%) were other melanoma types, including 12.5% (2/16) acral, 31.3% (5/16) mucosal and 56.3% (9/16) NCSD melanomas. No DLTs were observed in both Part A and B. In Part A, 9 pts occurred treatment-related adverse events (TRAEs), most commonly pruritus (4 pts), blood thyroid stimulating hormone increased (2 pts), and asthenia (2 pts). No AEs of ≥ grade 3 were reported. Five pts had stable disease (SD). In Part B and C, 13 pts reported TRAEs, only 1 pt occurred grade 3 TRAE (aspartate aminotransferase increased in 3mg dose level), and others reported grade 2, most commonly pruritus (8 pts), rash (7 pts) and alanine aminotransferase increased (6 pts). No AEs leading to death. In evaluable pts in combination with sintilimab, 1 (NCSD melanoma) of 7 pts (3 NCSD, 1 acral, 2 mucosal and 1 CSD melanoma) reached confirmed partial response (PR) in 2 mg group, and 1 (acral melanoma) of 3 pts (1 acral, 1 mucosal and 1 NCSD melanomas) reached confirmed PR in 3 mg group. Five pts had SD. Part C is currently ongoing. Conclusions: IBI310 monotherapy or in combination with sintilimab were well-tolerated without unanticipated AEs in pts with advanced melanoma. The data preliminarily demonstrate an antitumor activity of the combination therapy in previously treated advanced melanoma (acral and NCSD melanomas). Clinical trial information: NCT03545971 .
Safety of weight-based dosing of nivolumab with or without ipilimumab by body mass index (BMI) stratified by sex across 14 CheckMate clinical trials.
Authors: McQuade Jennifer Leigh , Hammers Hans J. , Furberg Helena , Engert Andreas , Andre Thierry , Blumenschein George , Tannir Nizar M. , Baron Ari David , Larkin James , El-Khoueiry Anthony B. , Carbone David Paul , Thomas John-Michael , Hennicken Delphine , Zoffoli Roberto , Reshef Daniel , Coffey Mary , Motzer Robert J. 
Published: May 2020

e15114 Background: Associations between obesity and cancer risk, prognosis, and therapeutic outcomes have been extensively researched. However, the impact of BMI on safety in patients receiving immunotherapy has not been well described. Methods: A descriptive, retrospective analysis examined associations between BMI (kg/m2) (underweight/normal, BMI < 25; overweight, 25 ≤ BMI < 30; obese, BMI ≥ 30) and incidence of any-grade and grade 3/4 immune-mediated adverse events (imAEs) in patients receiving ≥ 1 dose of nivolumab 3 mg/kg as monotherapy (NIVO3; n = 2746). Data were pooled from CheckMate clinical trials across 8 tumor types. Data from nivolumab in combination with ipilimumab cohorts (n = 1026) and safety analyses by specific imAEs and tumor types will be presented. Results: Select NIVO3 monotherapy cohort patient demographics were: 68.5% male, median age of 61 years, median 10 doses received, and median BMI of 25.3 kg/m2. Results showed a trend towards higher incidence of any-grade, but not grade 3/4, imAEs in obese vs overweight and obese vs underweight/normal BMI patients (Table). BMI associations with imAE incidence were consistent with the overall trend across pre-defined subsets, including smoking status, age, and ECOG performance status. Both male and female patients had an increased incidence of any-grade imAEs with obesity; however, obese female patients had a higher incidence of grade 3/4 imAEs vs underweight/normal BMI (Table). Conclusions: This was a novel analysis of BMI and safety in 2746 patients across 8 tumor types in CheckMate clinical trials who were treated with nivolumab monotherapy. While obese patients showed a trend towards higher incidence of any-grade imAEs than those with overweight and underweight/normal BMI, incidence of grade 3/4 imAEs was consistent across BMI categories. Clinical trial information: CheckMate 017,026,057,025,039,205,040,066,067,141,275,142,016,214 (NCT numbers do not fit in field) . [Table: see text]
Immune checkpoint inhibitors combined with chemotherapy/radiotherapy, for EGFR wild-type lung cancer: Efficacy in real-world study.
Authors: Feng Jifeng , Shi Yue 
Published: May 2020

e15117 Background: The role of immune checkpoint inhibitors (anti-PD-1 antibody, ICI) combined with chemotherapy/radiotherapy for EGFR wild-type lung cancer is controversial, especially in 2nd-line or later treatment. The purpose of this study was to investigate the possible beneficial factors for immunotherapy for EGFR wild-type lung cancer. Methods: A total of 279 patients with EGFR wild-type lung cancer who received ICI were retrospectively analyzed, including 138 adenocarcinoma, 76 squamous carcinoma and 31 SCLC patients. Beneficial factors were determined by multivariable Cox proportional hazards model for PFS. PFS and ORR were compared between different therapies. Results: The specific results are shown in table. In multivariable analysis, ICI combined radiotherapy (P = 0.018; HR, 0.152(95% CI: 0.032, 0.727)) was identified as an effective independent factor for EGFR wild-type lung adenocarcinoma. PFS in patients who received ICI combined radiotherapy was significantly longer than that in those who received ICI monotherapy ((p = 0.032; not reached vs. 9.6 m (95% CI: 5.627, 13.640))). Among lung adenocarcinoma patients who received ICI as 2nd-line treatment, patients treated by ICI combined chemotherapy showed more benefit than those treated by ICI monotherapy (P = 0.003; HR, 0.012(95% CI: 0.001, 0.213)).ICI combined chemotherapy can significantly prolong PFS compared with those treated by ICI monotherapy (p = 0.015; 14.3 m [95% CI: 8.711, 19.822] vs. 1.1 m (95% CI: 0.25, 1.883)) in the 2nd-line treatment. However, ORR showed no significant different between ICI monotherapy and ICI combined chemotherapy(P = 0.626). Conclusions: ICI combined with radiotherapy showed better result than those who didn’t receive radiotherapy for EGFR wild-type lung adenocarcinoma. The addition of chemotherapy to ICI for the 2nd-line treatment in EGFR wild-type lung adenocarcinoma patients seems get more clinical benefit than ICI monotherapy. [Table: see text]
Checkpoint inhibitor-associated immune-related adverse events as harbinger of favorable clinical outcome: Systematic review and meta-analysis.
Authors: Park Robin , Lopes da Silva Laércio , Saeed Anwaar 
Published: May 2020

e15129 Background: Recent studies have observed an association between immune-related adverse events (irAE) and favorable clinical outcomes in the setting of cancer treatment with immune checkpoint inhibitors (ICI). However, results have been variable and inconclusive. Therefore, we have conducted a pan-cancer meta-analysis evaluating the relationship between irAEs and clinical outcomes. Methods: The search included PubMed, Embase, and Web of Science from conception to 12.28.2019 as well as abstracts published in the ASCO and ESMO meetings from 2015 to 2019. Studies were included if ICI was used in advanced or metastatic cancer settings and excluded if data contained only combination therapy regimens or contained anti-CTLA-4. Pooled sensitivity (SN), specificity (SP), positive (PPV) and negative predictive values (NPV), and odds ratios (ORs) were calculated using the 2 x 2 table and logit transformed proportions; and summary receiver operating curve (sROC) was generated using the bivariate approach for ORR. Pooled HRs were calculated using the means weighted by inverse of the variance for OS and PFS. Heterogeneity was assumed and random effects model was used throughout analyses. Results: Final analysis included 32 studies encompassing non-small cell lung cancer, melanoma, gastric cancer, renal cell carcinoma, urothelial carcinoma, and head and neck cancer. With respect to ORR, pooled SN, SP, PPV and NPV, and OR were 0.522 [0.423-0.619], 0.810 [0.771-0.844], 0.516 [0.413-0.618], 0.819 [0.764-0.864], and 4.59 [3.24-6.50] respectively. The area under the curve (AUC) derived from the sROC was 0.773. HR for OS and PFS were 0.47 [95% CI 0.37-0.60] and 0.46 [95% CI 0.37-0.56] respectively. Between-study publication bias was present for ORR, OS, and PFS but results remained significant after trim-fill analysis. Conclusions: irAEs predict OR, OS, and PFS across different types of cancer and may represent useful biomarkers in the clinical setting. [Table: see text]
Cardiotoxicity associated with immune checkpoint inibitors: A systemic review and meta-analysis.
Authors: Ba Aqeel Sheeba Habeeb , Lingamaneni Prasanth , Banskota Shristi Upadhyay , Farooq Muhammad Zain , Pichardo Rayli , Vohra Ishaan , Mangla Ankit 
Published: May 2020

e15131 Background: Immune checkpoint inhibitors (ICI) are associated with multiple immune related adverse events (irAE). Cardiotoxicities are rare but fatal complications. Since PD-1 and PD-L1 are expressed on human cardiomyocyte, there is an increased risk of cardiotoxicity with use of ICI. We performed a systematic review and meta-analysis to assess cardiotoxicities associated with PDL1 and CTLA4 inhibitors. Methods: The Embase, Ovid, Pubmed and Scopus were searched from inception to 2019 by two independent reviewers. All Phase II and III clinical trials reporting cardiotoxicities with the combination of, or monotherapy with anti-PD-1/PD-L1 and/or anti-CTLA4 were included. Our primary outcome was assessment of cardiotoxicity of all grades that included, hypertension, arrythmias, pericardial effusion, myocardial infarction, myocarditis, cardiomyopathy and cardiac arrest. Statistical heterogeneity was quantified using I2 statistics. The publication bias was assessed with Eggers regression test. The estimates were reported as odds Ratio (OR) with 95% confidence intervals (CI) using random effect model. Results: A total of 2,876 trials retrieved in the initial database search were analyzed according to PRISMA guidelines. Twenty trials met the inclusion criteria and were included in the final analysis. A total of 8,905 patients were included in these trials. There was no statistically significant difference in reported overall cardiotoxicity with ICI compared to placebo or standard of care (OR 0.953 95% CI 0.542-1.675, I2 89.49 p < 0.001). Also, no statistical significance associated with myocardial infarction (OR 0.76, 95% CI 0.76-3.298 I2 0%, P = 0.83), pericardial effusion (OR 1.44, 95% CI 0.72-2.90. I2= 0%, P = 0.613) or hypertension (OR 0.543, 95% CI 0.219-1.346. I2 = 94.98, P < 0.001). Myocarditis was reported in 8 patients with a statistically non-significant increased risk compared to standard of care or placebo (OR 2.16, 95% CI 0.719-6.828 I2= 0%, P = 0.885). Other reported cardiac irAE included cardiac arrest in 4 patients, QT prolongation in 2 patients and cardiac tamponade in 1 patient. Conclusions: The overall risk of cardiac related irAE is not significantly higher with ICI when compared with placebo or standard of care. The reported events of severe cardiac irAE like myocarditis and cardiac arrest are very low in the reported trials.
The safety and efficacy of immune-checkpoint inhibitor therapy in HIV infected cancer patients.
Authors: Myint Phyo Thazin , Ali Faisal S. , Verghese Dhiran , Alrifai Taha , Thet Aye Mon , Kozma Kelley Elizabeth 
Published: May 2020

e15141 Background: The clinical utility and safety of immune-checkpoint inhibitors (ICIs) in HIV infected cancer patients has not been well studied. Methods: We conducted a systematic search of Medline and Embase from inception to December 2019 to identify case reports and case series of ICI use in HIV infected cancer patients. Data were pooled utilizing a pre-specified protocol, and descriptive statistics were employed to report findings. Results: We identified 79 cases with a mean age of 52.5 (SD 11.65), 50 of whom were males. The most common cancers were NSCLC followed by Melanoma. Nivolumab was used in 54 patients whereas Pembrolizumab was used in 15 patients, with a mean of 25.7 months to ICI initiation from cancer diagnosis, and with a mean of 1.6 prior systemic lines of chemotherapy. 72 patients were on antiretroviral therapy. The mean baseline CD4 count was 385 (227.03), with a median baseline viral load of 40 (IQR 10.75-95.39). Mean CD4 count and median viral load during ICI therapy were 344.87 (SD 209.7) and 20 (0-400), respectively. 28 patients experienced and irAE; 63.2% and 63.6% of patients who experienced a decreased or increased CD4 count while on ICI therapy experienced an irAE, respectively. 27 patients experienced progressive disease (PD); 50% of patients who experienced a decrease in their CD4 count while on ICI therapy had PD. 13 patients experienced a complete response to ICI therapy; none of the patients who had a decreased CD4 count while on ICI therapy achieved complete response to ICI therapy, whereas 25% and 33% of patients who had an increased and stable CD4 count while ICI therapy experienced a complete response to therapy. The mortality rate was 24; 75% of patients who had a decreased CD4 count on ICI therapy suffered mortality, as opposed to 37.5% and 20% of patients with increased or stable CD4 count while on ICI therapy, respectively. Conclusions: Patients with a declining CD4 count while on ICI therapy may have poor outcomes with ICI therapy. The current body of evidence is weak, and further studies are needed to reach to a strong conclusion.
Inmunotherapy related hepatitis: A retrospective study of Chilean patients.
Authors: Salinas Carlos , Samtani Suraj Rajesh , Renner Alex , Aren Osvaldo Rudy , Rojas Carlos , Burotto Pichun Mauricio Emanuel 
Published: May 2020

e15144 Background: Immune checkpoint inhibitors (ICI) have shown dramatic efficacy in many trials of advanced solid cancer. Data of toxicity for these agents setting in Chilean patients is lacking and is of importance to confirm the tolerance of immunotherapy in different population. Immunotherapy-related hepatitis (liver irAEs) represents a diagnostic and management challenge, and its frequency varies according to various factors. We aim to report the incidence, features and treatments used to manage liver irAEs in Chilean population. Methods: A retrospective review of 139 patients with diagnosis of NSCLC, Renal Cancer, Urothelial, Melanoma, treated with ICI from April 2013 until November 2019. Baseline clinical factors (age, ECOG score, cancer type, stage, Type and number of cycles of immunotherapy, comorbidities), biochemistries and treatment received were recorded for all patients with liver irAEs. Checkpoint-inhibitor-associated liver disease was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) V.4 Treatment outcomes were analyzed by measuring progression free (PFS) and overall survival (OS). Results: 32 (23%) patients developed liver irAEs. Median age at diagnosis was 62 years (range 37-86). 62% patients were male, 59% ECOG 1, 96% had de novo metastatic disease. The most frequent primary sites of cancer were Renal Cancer 71% and NSCLC 9%. 78% of patients received treatment with both anti-PD-1/PD-L1 and CTLA-4 drugs. Liver irAEs G2 and G3 were 43.7% and 56.2% respectively. 31,2% and 12,5% of patients treated with single agent immunotherapy developed G2 and G3 Liver irAEs respectively. The total averages of cycles administered were 12, 4 cycles. 28% of patients developed liver irAEs after the first cycle of treatment and 12.5% after the second cycle. 6.2% patients required hospitalization and 78.1% required treatment with steroids. Conclusions: Liver irAEs was more frequent in Chilean population than data reported on previous clinical trials with a high incidence caused by ICI monotherapy and further reinforced by combination therapy. Local registries play an important role in recognizing different patterns of toxicity according to different population. Early recognition and management of liver irAEs should be of vital importance in clinical practice and as prescribing physicians we must maintain strict vigilance of liver irAES in Chilean population.
Checkpoint inhibitors related renal vasculitis and use of rituximab.
Authors: Mamlouk Omar , Lin Jamie , Tchakarov Amanda , Glass William F , Abdelrahim Maen , Selamet Umut , Buni Maryam , Abdelwahab Noha , Abudayyeh Ala 
Published: May 2020

e15145 Background: As the percentage of cancer patients eligible for checkpoint inhibitor therapy (CPI) is increasing rapidly over the past couple years and approaching 45%, more cases of CPI related nephrotoxicity, including a rare subset with vasculitis, are reported. To learn more about the clinical presentation of CPI associated renal vasculitis, its mechanism, treatment options, and prognosis, we describe cases from our institution and reviewed the literature for related cases. Methods: We retrospectively reviewed the charts of all cancer patients from 2014 to 2020 who were diagnosed with CPI related nephrotoxicity and underwent a kidney biopsy. Results: We identified 6 cases of renal vasculitis reach with different malignancy, 4 had pauci-immune GN and one of which had IgA vasculitis. 4 of the patients were on nivolumab and 4 of the patients had negative ANCA serology. All patients had microscopic hematuria and severe acute kidney injury (AKI) with Creatinine > 4.5 mg/dl upon diagnosis and 2 patients requiring renal replacement therapy (RRT). One patient had concurrent lung involvement. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. 3 patients received plasmapheresis who required RRT or had lung involvement. 2 patients died within 8 months of diagnosis due to malignancy progression and none of the cases had a relapse of vasculitis. Conclusions: We demonstrated that CPI can be associated with different types of renal vasculitis that is predominantly ANCA negative and manifest as severe kidney. Despite the lack of strong evidence, treatment as primary ANCA vasculitis with corticosteroids and rituximab is well tolerated with favorable renal outcome.
Baseline blood parameters as predictive biomarkers of immunotherapy efficacy in solid tumors.
Authors: Marra Antonio , Criscitiello Carmen , Morganti Stefania , Viale Giulia , Zagami Paola , Nicolò Eleonora , Ferraro Emanuela , Repetto Matteo , Tarantino Paolo , D'amico Paolo , Trapani Dario , Locatelli Marzia Adelia , Esposito Angela , Curigliano Giuseppe 
Published: May 2020

e15147 Background: Peripheral blood parameters, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and LDH level, have been correlated to immunotherapy (IO) benefit in melanoma and lung cancer. We investigated if peripheral blood parameters could have the same predictive role in a variety of solid tumors treated with either single-agent IO or IO combinations. Methods: Baseline (0 to 14 days from treatment start) blood parameters, including NLR, dNLR, PLR, LMR and LDH, were collected in patients (pts) with metastatic solid tumors treated in phase I trials testing anti-PD-1/PD-L1 single agent (N = 59) and anti-PD-1/PD-L1-based combinations (N = 94), including combinations with immune checkpoint inhibitors/agonists or other agents. IO benefit was assessed for overall survival (OS), progression free survival (PFS), overall response rate (ORR), disease control rate (DCR), and 90-day mortality rate. Logistic regression, Kaplan-Meier method, and Cox regression were carried out to evaluate the impact of clinical and baseline blood parameters on IO efficacy. Results: From Aug2014 to May2019, 153 pts were included [median age 58 (32-80)]. Female/male ratio was 1.47:1 (91 females/62 males). The most common tumors were gastrointestinal, breast, and gynecological cancers (22.9%, 22.2%, and 15.0%, respectively). Sixty pts (39.2%) had received more than two lines of therapy. Overall, ORR, DCR, and 90-day mortality were 11.8%, 34.9%, and 15.7%, respectively. At multivariate analysis, LDH higher than upper limit of normal (ULN) was associated with reduced DCR (LDH ≤ULN vs > ULN: 50.8% vs 20.8%, OR 0.25, 95%CI 0.1-0.62, p = .003) and increased 90-day mortality (LDH ≤ULN vs > ULN: 7.9% vs 24.5%, OR 3.59, 95%CI 1.18-10.9, p = .025). At a median follow-up of 25.9 months (22.3-29.6), 138 pts (90.2%) experienced tumor progression and 117 (77.0%) had died. At multivariate Cox regression analysis, LDH > ULN and dNLR > 3 were independently associated with reduced PFS (LDH > ULN: HR 1.97, 95%CI 1.30-2.99, p < .001; dNLR > 3: HR 2.29, 95%CI 1.39-3.77, p < .001) and reduced OS (LDH > ULN: HR 2.04, 95%CI 1.26-3.28, p = .004; dNLR > 3: HR 2.06, 95%CI 1.12-3.79, p = .02). Conclusions: Our analysis confirms that baseline LDH > ULN and dNLR > 3 are predictive biomarkers for IO efficacy, regardless of tumor type and combinations with other drugs, representing an easy tool that deserves prospective validation in IO-based clinical trials.