Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 11

Publication Record

Connections

Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors.
Vozy A, De Martin E, Johnson DB, Lebrun-Vignes B, Moslehi JJ, Salem JE
(2019) Eur J Cancer 123: 112-115
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, B7-H1 Antigen, CTLA-4 Antigen, Chemical and Drug Induced Liver Injury, Child, Databases, Factual, Female, Hepatitis, Autoimmune, Humans, Ipilimumab, Male, Massive Hepatic Necrosis, Middle Aged, Neoplasms, Nivolumab, Programmed Cell Death 1 Receptor, World Health Organization, Young Adult
Added November 12, 2019
0 Communities
1 Members
0 Resources
23 MeSH Terms
Individualised axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: a multicentre, single-arm, phase 2 study.
Ornstein MC, Pal SK, Wood LS, Tomer JM, Hobbs BP, Jia XS, Allman KD, Martin A, Olencki T, Davis NB, Gilligan TD, Mortazavi A, Rathmell WK, Garcia JA, Rini BI
(2019) Lancet Oncol 20: 1386-1394
MeSH Terms: Aged, Algorithms, Antineoplastic Agents, Antineoplastic Agents, Immunological, Axitinib, Carcinoma, Renal Cell, Dehydration, Diarrhea, Fatigue, Female, Humans, Hypertension, Ipilimumab, Kidney Neoplasms, Male, Middle Aged, Nivolumab, Progression-Free Survival, Response Evaluation Criteria in Solid Tumors, Retreatment
Show Abstract · Added October 30, 2019
BACKGROUND - Checkpoint inhibitor therapy is a standard of care for patients with metastatic renal cell carcinoma. Treatment options after checkpoint inhibitor therapy include vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors, although no prospective data regarding their use in this setting exist. Axitinib is a VEGF-R inhibitor with clinical data supporting increased activity with dose titration. We aimed to investigate the activity of dose titrated axitinib in patients with metastatic renal cell carcinoma who were previously treated with checkpoint inhibitor.
METHODS - We did a multicentre, phase 2 trial of axitinib given on an individualised dosing algorithm. Patients at least 18 years of age with histologically or cytologically confirmed locally recurrent or metastatic renal cell carcinoma with clear cell histology, a Karnofsky Performance Status of 70% or more, and measurable disease who received checkpoint inhibitor therapy as the most recent treatment were eligible. There was no limit on number of previous therapies received. Patients received oral axitinib at a starting dose of 5 mg twice daily with dose titration every 14 days in 1 mg increments (ie, 5 mg twice daily to 6 mg twice daily, up to 10 mg twice daily maximum dose) if there was no axitinib-related grade 2 or higher mucositis, diarrhoea, hand-foot syndrome, or fatigue. If one or more of these grade 2 adverse events occurred, axitinib was withheld for 3 days before the same dose was resumed. Dose reductions were made if recurrent grade 2 adverse events despite treatment breaks or grade 3-4 adverse events occurred. The primary outcome was progression-free survival. Analyses were done per protocol in all patients who received at least one dose of axitinib. Recruitment has been completed and the trial is ongoing. This trial is registered with ClincalTrials.gov, number NCT02579811.
FINDINGS - Between Jan 5, 2016 and Feb 21, 2018, 40 patients were enrolled and received at least one dose of study treatment. With a median follow-up of 8·7 months (IQR 3·7-14·2), the median progression-free survival was 8·8 months (95% CI 5·7-16·6). Fatigue (83%) and hypertension (75%) were the most common all-grade adverse events. The most common grade 3 adverse event was hypertension (24 patients [60%]). There was one (3%) grade 4 adverse event (elevated lipase) and no treatment-related deaths occurred. Serious adverse events that were likely related to therapy occurred in eight (20%) patients; the most common were dehydration (n=4) and diarrhoea (n=2).
INTERPRETATION - Individualised axitinib dosing in patients with metastatic renal cell inoma previously treated with checkpoint inhibitors did not meet the prespecified threshold for progression free survival, but these data show that this individualised titration scheme is feasible and has robust clinical activity. These prospective results warrant consideration of axitinib in this setting.
FUNDING - Pfizer.
Copyright © 2019 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis.
Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, Kerneis M
(2019) N Engl J Med 380: 2377-2379
MeSH Terms: Abatacept, Aged, Antineoplastic Agents, Immunological, Female, Humans, Immunosuppressive Agents, Lung Neoplasms, Myocarditis, Myositis, Nivolumab, Programmed Cell Death 1 Receptor
Added November 12, 2019
0 Communities
1 Members
0 Resources
MeSH Terms
Immune checkpoint inhibitor-associated hypophysitis-World Health Organisation VigiBase report analysis.
Guerrero E, Johnson DB, Bachelot A, Lebrun-Vignes B, Moslehi JJ, Salem JE
(2019) Eur J Cancer 113: 10-13
MeSH Terms: Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, B7-H1 Antigen, CTLA-4 Antigen, Databases, Factual, Female, Humans, Hypophysitis, Ipilimumab, Male, Middle Aged, Nivolumab, Pharmacovigilance, Programmed Cell Death 1 Receptor, World Health Organization, Young Adult
Added November 12, 2019
0 Communities
1 Members
0 Resources
20 MeSH Terms
Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma.
Beckermann KE, Jolly PC, Kim JY, Bordeaux J, Puzanov I, Rathmell WK, Johnson DB
(2017) J Immunother Cancer 5: 1
MeSH Terms: Adult, Antibodies, Monoclonal, Carcinoma, Medullary, Female, Humans, Kidney Neoplasms, Male, Neoplasm Metastasis, Nivolumab, Programmed Cell Death 1 Receptor, Tumor Microenvironment
Show Abstract · Added October 30, 2019
BACKGROUND - Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease. The role of immune system surveillance and responsiveness to anti-PD-1 therapies in RMC are completely unexplored.
CASE PRESENTATION - A 29 year old male with sickle cell trait presented with painless hematuria that ultimately resulted in a diagnosis of RMC. He underwent total nephrectomy and adjuvant cytotoxic chemotherapy with carboplatin, gemcitabine, paclitaxel, and bevacizumab. As is common in this aggressive form of kidney cancer he recurred with biopsy proven lymph node metastasis. He was started on checkpoint inhibitor therapy with nivolumab that inhibits program cell death protein 1 (PD-1), and on his first follow-up imaging he was found to have a partial response that on subsequent scans ultimately resulted in a complete response lasting greater than nine months. In this report, we present a patient with metastatic RMC who exhibited a clinical response to nivolumab, as well as the genetic and immunologic correlates of the pre-treatment tumor. Provocatively, robust immune infiltrate and expression of immune checkpoints were observed, despite the presence of a low mutation burden.
CONCLUSIONS - Here, we report the first case of immune microenvironment profiling and response to anti-PD-1 in a patient with RMC to our knowledge. This case suggests that anti-PD-1 based therapies may have clinical activity in RMC.
0 Communities
1 Members
0 Resources
MeSH Terms
Fulminant Myocarditis with Combination Immune Checkpoint Blockade.
Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA, Anders RA, Sosman JA, Moslehi JJ
(2016) N Engl J Med 375: 1749-1755
MeSH Terms: Aged, Antibodies, Monoclonal, Arrhythmias, Cardiac, Electrocardiography, Fatal Outcome, Female, Glucocorticoids, Heart Block, Humans, Immunotherapy, Ipilimumab, Male, Melanoma, Middle Aged, Myocarditis, Myocardium, Myositis, Nivolumab
Show Abstract · Added March 26, 2017
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).
0 Communities
5 Members
0 Resources
18 MeSH Terms
Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.
de Velasco G, Miao D, Voss MH, Hakimi AA, Hsieh JJ, Tannir NM, Tamboli P, Appleman LJ, Rathmell WK, Van Allen EM, Choueiri TK
(2016) Cancer Immunol Res 4: 820-822
MeSH Terms: Antibodies, Monoclonal, Antineoplastic Agents, Carcinoma, Renal Cell, Gene Expression Regulation, Neoplastic, Humans, Kidney Neoplasms, Mutation, Nivolumab, Prognosis, RNA, Neoplasm
Show Abstract · Added October 30, 2019
Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here, we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole-exome transcriptome data in renal cell carcinoma patients (n = 54) included in The Cancer Genome Atlas who ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by the MSKCC risk group, nor was the expression of cytolytic genes-granzyme A and perforin-or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis revealed that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. Cancer Immunol Res; 4(10); 820-2. ©2016 AACR.
©2016 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
MeSH Terms
Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy.
Johnson DB, Estrada MV, Salgado R, Sanchez V, Doxie DB, Opalenik SR, Vilgelm AE, Feld E, Johnson AS, Greenplate AR, Sanders ME, Lovly CM, Frederick DT, Kelley MC, Richmond A, Irish JM, Shyr Y, Sullivan RJ, Puzanov I, Sosman JA, Balko JM
(2016) Nat Commun 7: 10582
MeSH Terms: Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Genes, MHC Class II, Genotype, Humans, Melanoma, Nivolumab, Programmed Cell Death 1 Receptor, RNA, Messenger
Show Abstract · Added January 30, 2016
Anti-PD-1 therapy yields objective clinical responses in 30-40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFNγ-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of 'PD-1 signalling', 'allograft rejection' and 'T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4(+) and CD8(+) tumour infiltrate. MHC-II(+) tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection.
4 Communities
7 Members
0 Resources
11 MeSH Terms
Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS
(2014) J Clin Oncol 32: 1020-30
MeSH Terms: Adult, Antibodies, Monoclonal, Antineoplastic Agents, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Male, Melanoma, Middle Aged, Nivolumab, Skin Neoplasms, Survival Rate
Show Abstract · Added March 20, 2014
PURPOSE - Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued.
PATIENTS AND METHODS - Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation.
RESULTS - Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative.
CONCLUSION - Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy.
Johnson DB, Wallender EK, Cohen DN, Likhari SS, Zwerner JP, Powers JG, Shinn L, Kelley MC, Joseph RW, Sosman JA
(2013) Cancer Immunol Res 1: 373-7
MeSH Terms: Adult, Aminoquinolines, Anaphylaxis, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Drug Eruptions, Female, Guillain-Barre Syndrome, Humans, Imiquimod, Indoles, Melanoma, Middle Aged, Nivolumab, Programmed Cell Death 1 Receptor, Skin Neoplasms, Sulfonamides, Vemurafenib
Show Abstract · Added March 20, 2014
Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and appear to be highly active clinically with favorable toxicity profiles. We report two patients with BRAF V600E mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multi-organ injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy (AIDP) and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent.
0 Communities
2 Members
0 Resources
18 MeSH Terms