scholarly journals Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma

Oncotarget ◽  
2015 ◽  
Vol 6 (38) ◽  
pp. 41228-41236 ◽  
Author(s):  
Liang Wang ◽  
Hua Wang ◽  
Hao Chen ◽  
Wei-da Wang ◽  
Xiao-qin Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Treatment Response ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Predict Treatment Response

scholarly journals Prognostic implications of PD-L1 expression in patients with angiosarcoma

2021 ◽  
pp. FSO691
Author(s):  
Jii Bum Lee ◽  
Beung-Chul Ahn ◽  
Seung Hyun Kim ◽  
Young Han Lee ◽  
Jung Woo Han ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Prognostic Biomarker ◽  
Progression Free Survival ◽  
Limited Data ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Median Progression Free Survival ◽  
Programmed Death ◽  
Prognostic Implications

Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma. Patients & methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019. Results: Thirteen (19%) patients had PD-L1 expression. Metastatic angiosarcoma patients who were PD-L1-negative (n = 24) showed longer median progression-free survival (4.9 vs 1.6 months; p = 0.04) and median overall survival (OS; 10.9 vs 5.4 months; p = 0.01) than those who were PD-L1-positive (n = 4). PD-L1 status proved to be a significant factor for OS. Conclusion: Metastatic angiosarcoma patients with PD-L1 expression showed shorter survival. PD-L1 status is an independent prognostic factor for OS in metastatic angiosarcoma patients.

scholarly journals Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study

2019 ◽  
Vol 37 (23) ◽  
pp. 1997-2007 ◽  
Author(s):  
Radhakrishnan Ramchandren ◽  
Eva Domingo-Domènech ◽  
Antonio Rueda ◽  
Marek Trněný ◽  
Tatyana A. Feldman ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Classic Hodgkin Lymphoma ◽  
Immune Mediated ◽  
Programmed Death

PURPOSE Nivolumab, an anti–programmed death-1 monoclonal antibody, has demonstrated frequent and durable responses in relapsed/refractory classic Hodgkin lymphoma (cHL). We report results from Cohort D of the CheckMate 205 trial, which assessed nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) for newly diagnosed cHL. METHODS Patients 18 years of age or older with untreated, advanced-stage (defined as III to IV and IIB with unfavorable risk factors) cHL were eligible for Cohort D of this multicenter, noncomparative, phase II trial. Patients received nivolumab monotherapy for four doses, followed by 12 doses of N-AVD; all doses were every 2 weeks, and nivolumab was administered at 240 mg intravenously. The primary end point was safety. Efficacy end points included objective response rate and modified progression-free survival, defined as time to disease progression/relapse, death, or next therapy. Chromosome 9p24.1 alterations and programmed death-ligand 1 expression were assessed in Hodgkin Reed-Sternberg cells in evaluable patients. RESULTS A total of 51 patients were enrolled and treated. At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater. Overall, 59% experienced a grade 3 to 4 treatment-related adverse event. Treatment-related febrile neutropenia was reported in 10% of patients. Endocrine immune-mediated adverse events were all grade 1 to 2 and did not require high-dose corticosteroids; all nonendocrine immune-mediated adverse events resolved (most commonly, rash; 5.9%). At the end of therapy, the objective response rate (95% CI) per independent radiology review committee was 84% (71% to 93%), with 67% (52% to 79%), achieving complete remission (five patients [10%] were nonevaluable and counted as nonresponders). With a minimum follow-up of 9.4 months, 9-month modified progression-free survival was 92%. Patients with higher-level Hodgkin Reed-Sternberg programmed death-ligand 1 expression had more favorable responses to N-AVD ( P = .041). CONCLUSION Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.

scholarly journals The Prognostic Value of Circulating Soluble Programmed Death Ligand-1 in Cancers: A Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Pei Huang ◽  
Wei Hu ◽  
Ying Zhu ◽  
Yushen Wu ◽  
Huapeng Lin
Keyword(s):  
Cancer Patients ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Dynamic Monitoring ◽  
Survival Prognosis ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

BackgroundStudies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results.ObjectiveThis meta-analysis was performed to assess the association between sPD-L1 and the prognosis of cancer patients.MethodsPublished articles in Pubmed, EMBASE, and Cochrane clinical trial databases were searched from the inception to September 2020. Overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) data were evaluated using a hazard ratio (HR) at 95% confidence interval (95% CI).ResultsA total 31 studies involving 17 tumors and 3,780 patients were included. The overexpression of sPD-L1 was associated with shorter OS (HR 1.85, 95% CI 1.59–2.15, I2 = 33%). High sPD-L1 had worse PFS (HR 2.40, 95% CI 1.55–3.72, I2 = 83%), and worse DFS (HR 2.92, 95% CI 2.02–4.29, I2 = 40%), without significant statistical difference in RFS (HR 2.08, 95% CI 0.99–4.40, I2 = 0%).ConclusionsHigh sPD-L1 levels were associated with worse survival prognosis in cancer patients. The sPD-L1 may be a potential prognostic, non-invasive, and dynamic monitoring biomarker for cancers in the future.

scholarly journals Prognostic Role of Soluble Programmed Death Ligand 1 in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Guixiang Liao ◽  
Zhihong Zhao ◽  
Yuting Qian ◽  
Xiean Ling ◽  
Shanyi Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Prognostic Role ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

ObjectiveThe objective of this study was to explore whether soluble programmed death ligand 1 (sPD-L1) is a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC).MethodsA comprehensive search of electronic databases was carried out. Original studies with inclusion of sPD-L1, progression-free survival, and overall survival in NSCLC were eligible. The primary endpoints were overall survival and progression-free survival. Hazard ratios (HRs) and 95% confidence intervals (CIs) were applied for data analysis.ResultsEight studies involving 710 patients with NSCLC were included in the analysis. A pooled data analysis revealed that high levels of sPD-L1 were correlated with poorer overall survival (HR = 2.34; 95% CI = 1.82–3.00; P < 0.001) and progression-free survival (HR = 2.35; 95% CI = 1.62–3.40, P < 0.001). A subgroup analysis revealed that high levels of sPD-L1 were correlated with poor overall survival in patients treated with immunotherapy (HR = 2.40; 95% CI = 1.79–3.22; P < 0.001).ConclusionThis pooled analysis of published data suggests that sPD-L1 may serve as a readily available biomarker for survival in NSCLC patients treated with ICI based treatment. Prospective studies with well-designed standard assessment methods should be conducted to validate the prognostic role of sPD-L1 in NSCLC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283177.

scholarly journals Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2969-2979 ◽  
Author(s):  
Naiyer A. Rizvi ◽  
Matthew D. Hellmann ◽  
Julie R. Brahmer ◽  
Rosalyn A. Juergens ◽  
Hossein Borghaei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Doublet Chemotherapy

Purpose Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non–small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC). Patients and Methods Patients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression-free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression. Results No dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression. Conclusion The safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%.

scholarly journals Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Min-Gu Kang ◽  
Eun-Jeong Won ◽  
Hyun-Woo Choi ◽  
Hye-Ran Kim ◽  
Hyun-Jung Choi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Clinical Outcome ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Serum Pth ◽  
The Relationship ◽  
Pth Level

We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1) pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (≥68.3 pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P=0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients.

scholarly journals Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial

Tumor Biology ◽  
2018 ◽  
Vol 40 (3) ◽  
pp. 101042831876400 ◽  
Author(s):  
Michael Nagel ◽  
Julia Schulz ◽  
Annett Maderer ◽  
Katrin Goepfert ◽  
Nadine Gehrke ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Treatment Response ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Cytokeratin 18 ◽  
Free Survival ◽  
Non Invasive ◽  
Third Line

Background: Gastric cancer is common malignancy and exhibits a poor prognosis. At the time of diagnosis, the majority of patients present with metastatic disease which precludes curative treatment. Non-invasive biomarkers which discriminate early from advanced stages or predict the response to treatment are urgently required. This study explored the cytokeratin-18 fragment M30 and full-length cytokeratin-18 M65 in predicting treatment response and survival in a randomized, placebo-controlled trial of advanced gastric cancer. Methods: Patients enrolled in the SUN-CASE study received sunitinib or placebo as an adjunct to standard therapy with leucovorin (Ca-folinate), 5-fluorouracil, and irinotecan in second or third line. Treatment response rates, progression-free survival and overall survival were assessed during a follow-up period of 12 months. Cytokeratin-18 fragments were analyzed in 52 patients at baseline and day 14 of therapy. Results: Levels of M30 correlated with the presence of metastasis and lymph node involvement and decreased significantly during chemotherapy. Importantly, baseline levels of M30 were significantly higher in patients who failed therapy. In addition, patients who did not respond to treatment were also identifiable at day 14 based on elevated M30 levels. By stepwise regression analysis, M30 at day 14 was identified as independent predictor of treatment response. Likewise, serum levels of full-length cytokeratin-18 M65 at baseline also correlated with treatment failure and progression-free survival. The addition of sunitinib did not exert any effects on serum levels of M30 or M65. Conclusion: The cytokeratin-18 fragment M30 at day 14 identifies patients that fail to second- or third-line therapy for advanced gastric cancer. Validation of this non-invasive biomarker in gastric cancer is warranted.

High Level of Soluble Interleukin-2 Receptor in Serum Predicts Treatment Resistance and Poor Progression Free Survival in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5332-5332
Author(s):  
Liang Wang ◽  
Zhongjun Xia
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Treatment Response ◽  
Conflicts Of Interest ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Enzyme Linked Immunosorbent Assay ◽  
Free Survival ◽  
High Level ◽  
Level Group

Abstract Background: The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment response and survival outcomes or not needs to be investigated in multiple myeloma (MM) patients. Methods: The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. 26 patients (32.1%) were treated with bortezomib-based regimens and 55 patients (67.9%) received old drugs-based regimens. Results: The mean concentration of sIL-2R for myeloma patients was 8.51ng/ml, significantly higher than that of healthy controls (0.56ng/ml, p<0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). 36 patients (44.4%) were classified as higher sIL-2R level group (>6.049ng/ml), and 45 patients (55.6%) as lower group (=<6.049ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, higher than that in higher level group (41.7%, p=0.156). The 3-year progression free survival (PFS) and overall survival (OS) rate was 16% and 64%, respectively. In a multivariate survival analysis including ECOG performance status score, treatment response, and sIL-2R level, it was found that all these three parameters were significantly independent prognostic factors for PFS (p=0.032, 0.016, and 0.043, respectively), but none factors maintained their value in predicting OS. Subgroup analysis revealed that high level of sIL-2R correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p=0.004). Conclusions: Serum sIL-2R level is a valuable biomarker for predicting treatment response and an independent prognostic factor for PFS, indicating novel drugs targeting the imbalance of IL-2/IL-2R system may be a promising strategy in MM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study

2017 ◽  
Vol 35 (19) ◽  
pp. 2117-2124 ◽  
Author(s):  
Andrea B. Apolo ◽  
Jeffrey R. Infante ◽  
Ani Balmanoukian ◽  
Manish R. Patel ◽  
Ding Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Phase Ib ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti–programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1–associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1–positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

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