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1.
Curr Oncol Rep ; 23(9): 100, 2021 07 16.
Article in English | MEDLINE | ID: mdl-34269922

ABSTRACT

PURPOSE OF REVIEW: Both anti-angiogenesis and immunotherapy are well-established therapeutic options in solid tumors. Here, we review the rationale as well as clinical evidence of combining these two approaches. RECENT FINDINGS: There is strong rationale and substantial preclinical and clinical evidence that anti-angiogenesis plays a pivotal role in overcoming immunotherapy resistance. The combination of an anti-angiogenic agent and a checkpoint inhibitor offers a more robust treatment option in many clinical trials in a wide variety of solid tumor types. Combination of anti-angiogenesis and immunotherapy has emerged as a standard of care in some tumor types and the indication is expected to expand to more tumor types in the years to come.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , Neovascularization, Pathologic/prevention & control , Tumor Microenvironment/drug effects , Animals , Clinical Trials as Topic , Drug Therapy, Combination , Humans , Immunotherapy/methods , Neoplasms/blood supply , Neoplasms/immunology , Outcome Assessment, Health Care , Survival Analysis , Tumor Microenvironment/immunology
2.
Perm J ; 242020.
Article in English | MEDLINE | ID: mdl-32097116

ABSTRACT

INTRODUCTION: Older age is a melanoma risk factor. Elderly individuals are likelier to have immunosenescence, which could help melanoma cells escape immune surveillance. Hence, it is believed that elderly people cannot mount a potent immune response to checkpoint inhibitors to eliminate melanoma. OBJECTIVES: To investigate age-related differences in the time to progression, overall survival, and immunotherapy-related adverse events among patients with metastatic melanoma who received checkpoint inhibitors. METHODS: We retrospectively identified patients at our institution between January 2012 and December 2016 with stage IV melanoma who received at least 1 dose of ipilimumab, pembrolizumab, nivolumab, or combined ipilimumab and nivolumab. Demographic, pathologic, and clinical characteristics were obtained. Immune-related response criteria were used to define responses. RESULTS: Twenty-nine patients were younger than age 65 years and 31 were age 65 years or older. Time to progression was comparable between the age groups (hazard ratio = 0.79, 95% confidence interval = 0.37-1.70, p = 0.46). Overall survival was not significantly different after immunotherapy between groups (hazard ratio = 0.75, 95% confidence interval = 0.31-1.82, p = 0.491). Overall, immunotherapy-related adverse events were comparable between groups, with 62% in younger patients (18/29) and 45% in older patients (14/31 p = 0.19). Of 60 patients, 30 responded to immunotherapy. Nonresponders were more likely than responders to have BRAF-mutated melanomas (16 [53.3%] vs 8 [27.6%]; p = 0.04) and less likely to have immunotherapy-related adverse events (12 [40%] vs 20 [66.7%]; p = 0.04). CONCLUSION: Aging does not seem to affect response to checkpoint inhibitors. Elderly patients with metastatic melanoma should be treated similarly to younger patients.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Ipilimumab/therapeutic use , Male , Melanoma/genetics , Melanoma/pathology , Middle Aged , Neoplasm Staging , Nivolumab/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Socioeconomic Factors , Survival Analysis
3.
Cancer Res ; 79(6): 1113-1123, 2019 03 15.
Article in English | MEDLINE | ID: mdl-30674537

ABSTRACT

Identifying controlling features of responsiveness to checkpoint blockade therapies is an urgent goal in oncology research. Our group and others have previously shown melanoma tumors resistant to checkpoint blockade display features of mesenchymal transition, including E-cadherin loss. Here, we present the first in vivo evidence that E-cadherin from tumor cells facilitate immune attack, using a B16F10 melanoma mouse model in which E-cadherin is exogenously expressed (B16.Ecad). We find, compared with vector control, B16.Ecad exhibits delayed tumor growth, reduced metastatic potential, and increased overall survival in vivo. Transplantation of B16.Ecad into Rag1-/- and CD103-/- mice abrogated the tumor growth delay. This indicates the anti-melanoma response against B16.Ecad is both immune and CD103+ mediated. Moreover, B16.Ecad showed increased responsiveness to combination immune checkpoint blockade (ICB) compared with vector control. This work establishes a rationale for ICB responses observed in high E-cadherin-expressing tumors and suggests therapeutic advancement through amplifying CD103+ immune cell subsets.Significance: These findings identify the mechanism behind checkpoint blockade resistance observed in melanoma that has undergone mesenchymal transition and suggest activation of CD103+ immune cells as a therapeutic strategy against other E-cadherin-expressing malignancies.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/6/1113/F1.large.jpg.


Subject(s)
Antigens, CD/metabolism , Antineoplastic Agents, Immunological/pharmacology , Cadherins/metabolism , Cell Cycle Checkpoints/drug effects , Integrin alpha Chains/metabolism , Lung Neoplasms/secondary , Melanoma, Experimental/pathology , Animals , Antigens, CD/genetics , Apoptosis , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Cadherins/antagonists & inhibitors , Cadherins/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Integrin alpha Chains/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Melanoma, Experimental/drug therapy , Melanoma, Experimental/immunology , Melanoma, Experimental/metabolism , Mice , Tumor Cells, Cultured , Tumor Microenvironment
4.
Onco Targets Ther ; 11: 7095-7107, 2018.
Article in English | MEDLINE | ID: mdl-30410366

ABSTRACT

Approximately 50% of melanomas harbor an activating BRAF mutation. Combined BRAF and MEK inhibitors such as dabrafenib and trametinib, vemurafenib and cobimetinib, and encorafenib and binimetinib are US Food and Drug Administration (FDA)-approved to treat patients with BRAF V600-mutated advanced melanoma. Both genetic and epigenetic alterations play a major role in resistance to BRAF inhibitors by reactivation of the MAPK and/or the PI3K-Akt pathways. The role of BRAF inhibitors in modulating the immunomicroenvironment and perhaps enhancing the efficacy of checkpoint inhibitors is gaining interest. This article provides a comprehensive review of mechanisms of resistance to BRAF and MEK inhibitors in melanoma and summarizes landmark trials that led to the FDA approval of BRAF and MEK inhibitors in metastatic melanoma.

5.
SAGE Open Med ; 6: 2050312118800202, 2018.
Article in English | MEDLINE | ID: mdl-30245818

ABSTRACT

OBJECTIVES: Our group developed the use of the Candida skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate cancer immunotherapy. METHODS: Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate cancer patients using interferon-γ enzyme-linked immunospot assay. RESULTS: The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides. CONCLUSION: In summary, a design and a formulation of a novel prostate cancer immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate cancer patients supports further development of this immunotherapy.

6.
Perm J ; 22: 17-181, 2018.
Article in English | MEDLINE | ID: mdl-30005721

ABSTRACT

INTRODUCTION: Basal cell carcinoma (BCC) is the most common skin cancer. It is primarily a local disease, and it very rarely causes metastatic disease. Chemotherapeutic agents had limited success in management of metastatic disease until the introduction of vismodegib. In this case report, we describe the presentation of a metastatic BCC that was not amenable to surgical resection or local treatment options and was treated successfully with vismodegib. CASE PRESENTATION: A 69-year-old white man was referred to our surgical clinic for evaluation of an erosive left shoulder lesion. Biopsy in the clinic showed BCC with evidence of metastases on positron emission tomography-computed tomography scan. Tumors had invaded multiple bony structures and multiple organs, making surgical resection not an option. The decision was made to treat the patient with vismodegib. At 1-year follow-up, the patient's left shoulder lesion had improved with no evidence of metabolically active distant metastasis. DISCUSSION: Although BCC is the most common skin cancer, it is usually a local disease and treated with local measures. Metastatic BCC is extremely rare, and in cases when surgical resection or local radiation are not viable options, chemotherapeutic agents typically offer very limited improvement. Vismodegib is an oral selective sonic hedgehog pathway inhibitor that shows benefit in patients with locally advanced or metastatic disease.


Subject(s)
Anilides/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Basal Cell/drug therapy , Pyridines/therapeutic use , Skin Neoplasms/drug therapy , Aged , Carcinoma, Basal Cell/diagnostic imaging , Humans , Male , Positron Emission Tomography Computed Tomography , Shoulder , Skin Neoplasms/diagnostic imaging
7.
J Psychosoc Oncol ; 36(4): 454-469, 2018.
Article in English | MEDLINE | ID: mdl-29863447

ABSTRACT

PURPOSE: The extent to which patients feel prepared for end-of-life (EOL) may be associated with important clinical outcomes. Despite growing interest in the concept of "preparedness," however, there is insufficient information about what cancer patients actually need to feel prepared. Such information is foundational for patient-centered care, theory-building, and instrument development. DESIGN: This qualitative study examined patient perspectives regarding preparedness for EOL care. PARTICIPANTS AND METHODS: In-depth interviews were conducted with patients with advanced malignancies and limited life expectancies. Participants were drawn from a large academic cancer center and had a diverse range of malignancies. Thematic text analysis was used to analyze the data. FINDINGS: Six overarching themes emerged. These included readiness to manage concerns about: (1) EOL planning (e.g., goals of care, location of care); (2) interactions with healthcare providers (e.g., communication, symptom control); (3) interactions with family/friends (e.g., perceived burden, support); (4) emotional well-being (e.g., existential distress, fulfillment); (5) spiritual well-being (e.g., spiritual comfort, congregational support); and (6) financial well-being (e.g., medical expenses, estate planning). CONCLUSIONS: Findings highlight areas that patients themselves regard as critical for a sense of preparedness for EOL care. Participants emphasized broader concerns than those previously construed as facets of patient preparedness, and these domains offer modifiable targets for intervention.


Subject(s)
Attitude to Health , Neoplasms/therapy , Patients/psychology , Terminal Care/psychology , Aged , Female , Humans , Male , Middle Aged , Patients/statistics & numerical data , Qualitative Research
8.
J Cancer Educ ; 33(1): 186-192, 2018 02.
Article in English | MEDLINE | ID: mdl-27516202

ABSTRACT

New educational methods and structures to improve medical education are needed to face the challenge of an exponential increase and complexity of medical knowledge. Collaborative learning has been increasingly used in education, but its use in medical training programs is in its infancy, and its impact is still unknown; the role of competition in education is more controversial. We introduced these pedagogical methods to the hematology/oncology fellowship program at the University of Arkansas for Medical Sciences to improve attendance and performance at didactic activities and different educational outcomes. One year after the adoption of these methods, the fellowship program has reached many of the expected goals from this intervention without the negative consequences of competition observed in younger learners. The most important conclusion of this project is that collaboration and cross-generational team work provide a healthy and effective learning environment and competition may not add further benefit. Analysis, interpretation, and discussion of our experience are provided. This study was approved by the University of Arkansas for Medical Sciences IRB as a low risk educational intervention not requiring a consent form.


Subject(s)
Education, Medical/methods , Fellowships and Scholarships/standards , Hematology/education , Integrative Medicine/standards , Interdisciplinary Placement , Learning , Medical Oncology/education , Humans
9.
J Oncol Pharm Pract ; 24(5): 389-392, 2018 Jul.
Article in English | MEDLINE | ID: mdl-28355971

ABSTRACT

Pembrolizumab, a selective anti-PD-1 humanized monoclonal antibody, reactivates T cells to fight cancer. Immune-related adverse events such as autoimmune colitis, pneumonitis, hepatitis, nephritis, hypophysitis, and thyroiditis may occur during, or weeks to months after therapy. Pemprolizumab-induced synovitis is rarely reported. With the wide use of immunotherapy to treat cancers, physicians need to be aware of this rare immune-related adverse event and provide immediate treatment to avoid permanent joint damage.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/adverse effects , Synovitis/chemically induced , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Agents/therapeutic use , Female , Humans , Immunotherapy , Melanoma/drug therapy , Middle Aged
10.
J Oncol Pharm Pract ; 24(6): 468-472, 2018 Sep.
Article in English | MEDLINE | ID: mdl-28625074

ABSTRACT

The field of gut microbiota is of growing interest, especially in the recent discoveries of its interaction with host immune responses, which when disrupted, can further alter immunity. It also plays a role in cancer development, its microenvironment and response to anticancer therapeutics. Several recently published experimental studies had explored the efficacy of modifying microbiota to enhance the response of checkpoint inhibitors, suggesting its beneficial function in cancer management and potential to be targeted as a therapeutic agent to enhance efficacy of checkpoint inhibitors. Here we review available evidence, mechanisms and hypotheses of its use to enhance cancer response.


Subject(s)
Antineoplastic Agents/therapeutic use , Gastrointestinal Microbiome , Neoplasms/drug therapy , Humans
11.
Case Rep Hematol ; 2018: 2464619, 2018.
Article in English | MEDLINE | ID: mdl-30671268

ABSTRACT

Ipilimumab is a monoclonal antibody that enhances the efficacy of the immune system by targeting a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which is a protein receptor that downregulates the immune system. Nivolumab is also a humanized monoclonal antibody that targets another protein receptor that prevents activated T cells from attacking the cancer; this receptor is called programmed cell death 1 (PD-1). The FDA approved ipilimumab combined with nivolumab as a frontline therapy for patients with metastatic melanoma or renal cell carcinoma and as a second-line therapy for patients with microsatellite instability-high (MSI-H) metastatic colon cancer. Immune-related adverse events such as autoimmune colitis, pneumonitis, hepatitis, nephritis, hypophysitis, and thyroiditis may occur during or weeks to months after therapy. We report a case of thrombotic thrombocytopenic purpura (TTP) in a patient with metastatic renal cell carcinoma following one cycle of ipilimumab and nivolumab. Only one case report of ipilimumab-induced TTP exists in the medical literature. With the wide use of immunotherapy to treat cancers, physicians need to be aware of this rare immune-related adverse event.

12.
Perm J ; 21: 17-004, 2017.
Article in English | MEDLINE | ID: mdl-28746020

ABSTRACT

INTRODUCTION: Programmed death receptor-1 blockade with pembrolizumab is approved by the US Food and Drug Administration to treat patients with metastatic melanoma. Activating T cells to fight cancer may cause immune-mediated adverse events. Pembrolizumab-induced pancytopenia has not been previously reported in the medical literature, to our knowledge. CASE PRESENTATION: A 52-year-old Caucasian woman with a diagnosis of metastatic melanoma of the rectum experienced multiple adverse events along her course of therapy with pembrolizumab, ranging from colitis, hepatitis, gastritis, and vitiligo after the fifth cycle of pembrolizumab; to knee synovitis after the 14th cycle; and to severe pancytopenia after the 18th cycle of pembrolizumab. Severe pancytopenia improved after high-dose corticosteroids and a 5-day course of intravenous immunoglobulin therapy. DISCUSSION: In our case, pembrolizumab-induced Grade 4 pancytopenia resolved via a combination of corticosteroids and intravenous immunoglobulins. Pancytopenia reached a nadir in 10 weeks, and it took 16 weeks for meaningful recovery.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Pancytopenia/chemically induced , Female , Humans , Middle Aged , Rectal Neoplasms/drug therapy , Rectal Neoplasms/secondary
13.
Perm J ; 21: 16-193, 2017.
Article in English | MEDLINE | ID: mdl-28633725

ABSTRACT

INTRODUCTION: Incidence of well-differentiated neuroendocrine tumors (NETs) of the colon and rectum is increasing and is now approximately 1 per 100,000 in the US. NETs are either well-differentiated (indolent) or poorly differentiated (aggressive). The majority of these tumors are found incidentally during screening colonoscopies and rarely are associated with symptoms of hormonal syndrome, even during the advanced stage. Metastatic well-differentiated NETs of the colon and rectum are incurable, hard to treat, and associated with a poor prognosis and survival rates similar to colorectal adenocarcinoma survival. CASE PRESENTATION: A 56-year-old man presented to our clinic with right-sided weakness and a 40-pound weight loss during the previous 2 months. A neurologic examination was remarkable for atrophy of the right trapezius muscle and decreased strength in the right upper extremity. Imaging revealed extensive blastic and lytic lesions involving the axial skeleton, a large rectal mass, a large necrotic nodal mass extending from the left iliac region to the level of the left renal veins, and multiple necrotic liver metastasis. Liver lesion fine-needle aspiration findings were consistent with metastatic well-differentiated neuroendocrine carcinoma. DISCUSSION: This case illustrates how a low-grade tumor can have an aggressive course with poor outcomes. Metastatic well-differentiated NETs of the colon and rectum remain difficult to treat because evidence is scarce. More research is needed on this topic.


Subject(s)
Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Disease Progression , Fatal Outcome , Humans , Liver/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Rectum/diagnostic imaging , Rectum/pathology , Tomography, X-Ray Computed
15.
Cancer Biol Ther ; 18(7): 451-469, 2017 Jul 03.
Article in English | MEDLINE | ID: mdl-28513269

ABSTRACT

Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the programmed death receptor-1 (PD1) has resulted in unprecedented durable responses in metastatic melanoma. However, resistance to immunotherapy remains a major challenge. Effective immune surveillance against melanoma requires 4 essential steps: activation of the T lymphocytes, homing of the activated T lymphocytes to the melanoma microenvironment, identification and episode of melanoma cells by activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis. At each of these steps, there are multiple factors that may interfere with the immune surveillance machinery, thus allowing melanoma cells to escape immune attack and develop resistance to immunotherapy. We provide a comprehensive review of the complex immune surveillance mechanisms at play in melanoma, and a detailed discussion of how these mechanisms may allow for the development of intrinsic or acquired resistance to immunotherapeutic modalities, and potential avenues for overcoming this resistance.


Subject(s)
Immunologic Surveillance , Melanoma/immunology , Tumor Escape/immunology , Animals , Apoptosis/genetics , Apoptosis/immunology , Cell Movement , Humans , Immunomodulation , Immunotherapy , Lymphocyte Activation/genetics , Lymphocyte Activation/immunology , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Melanoma/metabolism , Melanoma/pathology , Melanoma/therapy , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
16.
Sci Rep ; 7(1): 807, 2017 04 11.
Article in English | MEDLINE | ID: mdl-28400597

ABSTRACT

Modulation of the immune system can produce anti-tumor responses in various cancer types, including melanoma. Recently, immune checkpoint inhibitors (ICI), in single agent and combination regimens, have produced durable and long-lasting clinical responses in a subset of metastatic melanoma patients. These monoclonal antibodies, developed against CTLA-4 and PD-1, block immune-inhibitory receptors on activated T-cells, amplifying the immune response. However, even when using anti-CTLA-4 and anti-PD-1 in combination, approximately half of patients exhibit innate resistance and suffer from disease progression. Currently, it is impossible to predict therapeutic response. Here, we report the first proteomic and histone epigenetic analysis of patient metastatic melanoma tumors taken prior to checkpoint blockade, which revealed biological signatures that can stratify patients as responders or non-responders. Furthermore, our findings provide evidence of mesenchymal transition, a known mechanism of immune-escape, in non-responding melanoma tumors. We identified elevated histone H3 lysine (27) trimethylation (H3K27me3), decreased E-cadherin, and other protein features indicating a more mesenchymal phenotype in non-responding tumors. Our results have implications for checkpoint inhibitor therapy as patient specific responsiveness can be predicted through readily assayable proteins and histone epigenetic marks, and pathways activated in non-responders have been identified for therapeutic development to enhance responsiveness.


Subject(s)
Antibodies, Monoclonal/immunology , CTLA-4 Antigen/immunology , Drug Resistance, Neoplasm , Histone Code , Melanoma/drug therapy , Programmed Cell Death 1 Receptor/immunology , Antibodies, Monoclonal/therapeutic use , CTLA-4 Antigen/antagonists & inhibitors , Epithelial-Mesenchymal Transition , Humans , Melanoma/genetics , Melanoma/pathology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Proteome/metabolism , T-Lymphocytes/metabolism
18.
J Oncol Pharm Pract ; 23(3): 215-219, 2017 Apr.
Article in English | MEDLINE | ID: mdl-26811403

ABSTRACT

Immune therapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. Ipilimumab, nivolumab, and pembrolizumab are all FDA-approved immune checkpoint inhibitors to treat metastatic melanoma. Responses to immune checkpoint inhibitors are usually delayed. An interim progression on restaging computed tomography scans "pseudo-progression" may be observed before response to treatment occur. In this case, we report a significant interim progression of metastatic mucosal melanoma before meaningful responses to immunotherapy occurred. The patient developed significant immune therapy-related colitis and new onset vitiligo. Further restaging computed tomography scans showed sustained tumor response despite stopping the immune therapy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Melanoma/therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Female , Humans , Immunotherapy/methods , Ipilimumab , Middle Aged , Nivolumab
19.
J Oncol Pharm Pract ; 23(8): 620-624, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27590328

ABSTRACT

Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma. The adverse events of these medications are predominantly immune related. Sarcoidosis-like syndrome/lymphadenopathy represents a challenging adverse event to the oncologist as it can be mistaken for progressive disease. Hence, awareness of such adverse event and obtaining a biopsy of the enlarged lymph nodes will confirm the diagnosis and avoid the unnecessary change of current therapies for those with stage IV disease or adding new ones for those with stage III disease. We report three cases of immunotherapy-related sarcoidosis-like syndrome/lymphadenopathy; two cases occurred during adjuvant ipilimumab for stage III surgically resected melanoma and one case during pemprolizumab for stage IV metastatic melanoma.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Lymphadenopathy/chemically induced , Melanoma/drug therapy , Sarcoidosis/chemically induced , Skin Neoplasms/drug therapy , Adult , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , CTLA-4 Antigen/antagonists & inhibitors , Female , Humans , Immunotherapy/methods , Ipilimumab/adverse effects , Lymphadenopathy/diagnostic imaging , Male , Melanoma/diagnostic imaging , Middle Aged , Nivolumab , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Sarcoidosis/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Melanoma, Cutaneous Malignant
20.
Perm J ; 20(3): 15-149, 2016.
Article in English | MEDLINE | ID: mdl-27352410

ABSTRACT

INTRODUCTION: Metastatic renal cell carcinoma (RCC) to the head and neck is rare. It is the third-most common cause of distant metastasis to the head and neck, after breast cancer and lung cancer. Several drugs are available to treat metastatic RCC including high-dose interleukin and targeted therapy. Immunotherapy with nivolumab was recently approved by the US Food and Drug Administration (FDA) as a second-line treatment for patients with metastatic RCC. CASE PRESENTATION: We present a case of metastatic RCC in a 71-year-old man with a single complaint of a 1-year history of pain while chewing food. Positron emission tomography-computed tomography showed diffuse metastatic disease. Nivolumab, off-label use before its recent FDA approval, was combined with sunitinib and resulted in an excellent and ongoing response. DISCUSSION: RCC is the third-most common cause of distant metastasis to the head and neck. The patient described in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease. The other important aspect of this case is the almost complete response of his metastatic disease to the combination of nivolumab and sunitinib that was used off label before the FDA issued the approval. Future clinical trials should look at combining immunotherapy with targeted therapy in metastatic RCC.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacology , Carcinoma, Renal Cell/etiology , Indoles/pharmacology , Kidney Neoplasms/pathology , Mastication/physiology , Neoplasm Metastasis , Pain , Pyrroles/pharmacology , Aged , Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols , Humans , Indoles/administration & dosage , Male , Neoplasm Metastasis/drug therapy , Nivolumab , Pyrroles/administration & dosage , Sunitinib , Treatment Outcome , United States
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