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Melanoma: HELP
Articles by Ahmad A. Tarhini
Based on 81 articles published since 2010
(Why 81 articles?)
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Between 2010 and 2020, A. A. Tarhini wrote the following 81 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline An update on the Society for Immunotherapy of Cancer consensus statement on tumor immunotherapy for the treatment of cutaneous melanoma: version 2.0. 2018

Sullivan, Ryan J / Atkins, Michael B / Kirkwood, John M / Agarwala, Sanjiv S / Clark, Joseph I / Ernstoff, Marc S / Fecher, Leslie / Gajewski, Thomas F / Gastman, Brian / Lawson, David H / Lutzky, Jose / McDermott, David F / Margolin, Kim A / Mehnert, Janice M / Pavlick, Anna C / Richards, Jon M / Rubin, Krista M / Sharfman, William / Silverstein, Steven / Slingluff, Craig L / Sondak, Vernon K / Tarhini, Ahmad A / Thompson, John A / Urba, Walter J / White, Richard L / Whitman, Eric D / Hodi, F Stephen / Kaufman, Howard L. ·Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. · Georgetown University, Washington, DC, 20057, USA. · University of Pittsburgh, Pittsburgh, PA, 15213, USA. · St. Luke's Cancer Center and Temple University, Center Valley, PA, 18034, USA. · Loyola University Medical Center, Maywood, IL, 60153, USA. · Roswell Park Cancer Institute, Buffalo, NY, 14263, USA. · University of Michigan, Ann Arbor, MI, 48109, USA. · University of Chicago Medical Center, Chicago, IL, 60637, USA. · Cleveland Clinic, Cleveland, OH, 44195, USA. · Emory Winship Cancer Institute, Atlanta, GA, 30322, USA. · Mt. Sinai Medical Center, Miami Beach, FL, 33140, USA. · Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA. · City of Hope, Duarte, CA, 91010, USA. · Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08901, USA. · New York University Cancer Institute, New York, NY, 10016, USA. · Lutheran General Hospital, Park Ridge, IL, 60068, USA. · The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21231, USA. · Melanoma Research Foundation, Woodcliff Lake, NJ, 07077, USA. · University of Virginia, Charlottesville, VA, 22908, USA. · H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. · Cleveland Clinic Taussig Cancer Center, Cleveland, OH, 44195, USA. · Seattle Cancer Care Alliance, Seattle, WA, 98109, USA. · Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213, USA. · Carolinas Medical Center, Charlotte, NC, 28204, USA. · Carol G. Simon Cancer Center, Morristown, NJ, 07046, USA. · Dana-Farber Cancer Institute, Boston, MA, 02215, USA. · Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. howardkaufman6@gmail.com. ·J Immunother Cancer · Pubmed #29848375.

ABSTRACT: BACKGROUND: Cancer immunotherapy has been firmly established as a standard of care for patients with advanced and metastatic melanoma. Therapeutic outcomes in clinical trials have resulted in the approval of 11 new drugs and/or combination regimens for patients with melanoma. However, prospective data to support evidence-based clinical decisions with respect to the optimal schedule and sequencing of immunotherapy and targeted agents, how best to manage emerging toxicities and when to stop treatment are not yet available. METHODS: To address this knowledge gap, the Society for Immunotherapy of Cancer (SITC) Melanoma Task Force developed a process for consensus recommendations for physicians treating patients with melanoma integrating evidence-based data, where available, with best expert consensus opinion. The initial consensus statement was published in 2013, and version 2.0 of this report is an update based on a recent meeting of the Task Force and extensive subsequent discussions on new agents, contemporary peer-reviewed literature and emerging clinical data. The Academy of Medicine (formerly Institute of Medicine) clinical practice guidelines were used as a basis for consensus development with an updated literature search for important studies published between 1992 and 2017 and supplemented, as appropriate, by recommendations from Task Force participants. RESULTS: The Task Force considered patients with stage II-IV melanoma and here provide consensus recommendations for how they would incorporate the many immunotherapy options into clinical pathways for patients with cutaneous melanoma. CONCLUSION: These clinical guidleines provide physicians and healthcare providers with consensus recommendations for managing melanoma patients electing treatment with tumor immunotherapy.

2 Guideline The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma. 2013

Kaufman, Howard L / Kirkwood, John M / Hodi, F Stephen / Agarwala, Sanjiv / Amatruda, Thomas / Bines, Steven D / Clark, Joseph I / Curti, Brendan / Ernstoff, Marc S / Gajewski, Thomas / Gonzalez, Rene / Hyde, Laura Jane / Lawson, David / Lotze, Michael / Lutzky, Jose / Margolin, Kim / McDermott, David F / Morton, Donald / Pavlick, Anna / Richards, Jon M / Sharfman, William / Sondak, Vernon K / Sosman, Jeffrey / Steel, Susan / Tarhini, Ahmad / Thompson, John A / Titze, Jill / Urba, Walter / White, Richard / Atkins, Michael B. ·Rush University Cancer Center, 1725 West Harrison Street, Chicago, IL 60612, USA. ·Nat Rev Clin Oncol · Pubmed #23982524.

ABSTRACT: Immunotherapy is associated with durable clinical benefit in patients with melanoma. The goal of this article is to provide evidence-based consensus recommendations for the use of immunotherapy in the clinical management of patients with high-risk and advanced-stage melanoma in the USA. To achieve this goal, the Society for Immunotherapy of Cancer sponsored a panel of melanoma experts--including physicians, nurses, and patient advocates--to develop a consensus for the clinical application of tumour immunotherapy for patients with melanoma. The Institute of Medicine clinical practice guidelines were used as a basis for this consensus development. A systematic literature search was performed for high-impact studies in English between 1992 and 2012 and was supplemented as appropriate by the panel. This consensus report focuses on issues related to patient selection, toxicity management, clinical end points and sequencing or combination of therapy. The literature review and consensus panel voting and discussion were used to generate recommendations for the use of immunotherapy in patients with melanoma, and to assess and rate the strength of the supporting evidence. From the peer-reviewed literature the consensus panel identified a role for interferon-α2b, pegylated-interferon-α2b, interleukin-2 (IL-2) and ipilimumab in the clinical management of melanoma. Expert recommendations for how to incorporate these agents into the therapeutic approach to melanoma are provided in this consensus statement. Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted.

3 Editorial Vaccine therapy + dasatinib for the treatment of patients with stage IIIB-IV melanoma. 2016

Tarhini, Ahmad A / Tawbi, Hussein / Storkus, Walter J. ·Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. · Melanoma Program of the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. · Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. · Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. · Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. · Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. ·Melanoma Manag · Pubmed #30190895.

ABSTRACT: -- No abstract --

4 Editorial The future of systemic therapy of melanoma: combinations, predictive biomarkers. 2015

Tarhini, Ahmad A. · ·Oncology (Williston Park) · Pubmed #25683827.

ABSTRACT: -- No abstract --

5 Editorial How much of a good thing? What duration for interferon alfa-2b adjuvant therapy? 2012

Tarhini, Ahmad A / Kirkwood, John M. · ·J Clin Oncol · Pubmed #23008298.

ABSTRACT: -- No abstract --

6 Review Neoadjuvant therapy of locally/regionally advanced melanoma. 2019

Khunger, Arjun / Buchwald, Zachary S / Lowe, Michael / Khan, Mohammad K / Delman, Keith A / Tarhini, Ahmad A. ·Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, OH, USA. · Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA. · Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. · Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Comprehensive Cancer Center, 1365 Clifton Rd Atlanta, GA 30322, USA. ·Ther Adv Med Oncol · Pubmed #31391869.

ABSTRACT: Locally/regionally advanced melanoma confers a major challenge in terms of surgical and medical management. Surgical treatment carries the risks of surgical morbidities and potential complications that could be lasting. In addition, these patients continue to have a high risk of relapse and death despite the use of standard adjuvant therapy. Neoadjuvant therapy has the potential to significantly improve the clinical outcome of these patients, particularly in this era of newer and effective targeted and immunotherapeutic agents. Previous neoadjuvant studies tested chemotherapy with temozolomide where the clinical activity was limited. Biochemotherapy (BCT) was tested in two studies in the neoadjuvant setting and showed high tumor response rates; however, BCT was ultimately abandoned following its failure to demonstrate survival benefits in randomized trials of metastatic disease. Success of immunotherapy and targeted therapy in prolonging the lives of patients with metastatic melanoma generated considerable interest to investigate these novel strategies in the adjuvant and neoadjuvant settings. A number of neoadjuvant targeted and immunotherapy studies have been completed in melanoma to date and have yielded promising clinical activity. Given these encouraging results, a number of studies with other molecularly targeted and immunotherapeutic agents and their combinations are ongoing in the neoadjuvant setting; long-term outcome data are eagerly awaited. Such studies also provide access to biospecimens before and during therapy, allowing for the conduct of biomarker and mechanistic studies that may have a significant impact in guiding adjuvant therapy choices and drug development.

7 Review Predictive and on-treatment monitoring biomarkers in advanced melanoma: Moving toward personalized medicine. 2018

Tarhini, Ahmad / Kudchadkar, Ragini R. ·Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, United States. Electronic address: tarhina1@ccf.org. · Winship Cancer Institute of Emory University, 1365 Clifton Rd NE, Bldg C, Atlanta, GA 30322, United States. ·Cancer Treat Rev · Pubmed #30273812.

ABSTRACT: The treatment armamentarium for patients with metastatic melanoma has increased substantially over the past decade with the regulatory approval of targeted BRAF + MEK inhibitors and immune checkpoint inhibitors, which have vastly improved long-term outcomes. Recently, these advances have been rapidly translated to the high-risk adjuvant setting. Primary and acquired resistance to both immune and molecularly targeted agents, however, remains a challenge. Therefore, biomarkers predictive of response to therapy that can be assessed prior to initiation of treatment and early during the course of therapy are critical. Equally important is on-treatment biomarker monitoring that may predict the likelihood of treatment failure and disease relapse. This review will summarize recent advances in the understanding of biomarkers for patients with advanced melanoma, emphasizing emerging baseline predictive factors and on-treatment monitoring of biomarkers that aim to establish truly personalized treatment.

8 Review Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy. 2017

Johnson, Mariah M / Leachman, Sancy A / Aspinwall, Lisa G / Cranmer, Lee D / Curiel-Lewandrowski, Clara / Sondak, Vernon K / Stemwedel, Clara E / Swetter, Susan M / Vetto, John / Bowles, Tawnya / Dellavalle, Robert P / Geskin, Larisa J / Grossman, Douglas / Grossmann, Kenneth F / Hawkes, Jason E / Jeter, Joanne M / Kim, Caroline C / Kirkwood, John M / Mangold, Aaron R / Meyskens, Frank / Ming, Michael E / Nelson, Kelly C / Piepkorn, Michael / Pollack, Brian P / Robinson, June K / Sober, Arthur J / Trotter, Shannon / Venna, Suraj S / Agarwala, Sanjiv / Alani, Rhoda / Averbook, Bruce / Bar, Anna / Becevic, Mirna / Box, Neil / E Carson, William / Cassidy, Pamela B / Chen, Suephy C / Chu, Emily Y / Ellis, Darrel L / Ferris, Laura K / Fisher, David E / Kendra, Kari / Lawson, David H / Leming, Philip D / Margolin, Kim A / Markovic, Svetomir / Martini, Mary C / Miller, Debbie / Sahni, Debjani / Sharfman, William H / Stein, Jennifer / Stratigos, Alexander J / Tarhini, Ahmad / Taylor, Matthew H / Wisco, Oliver J / Wong, Michael K. ·Department of Dermatology, Oregon Health & Science University, 3303 SW Bond Ave., Portland, OR, USA. · University of Utah, Salt Lake City, UT, USA. · University of Washington, Seattle, WA, USA. · University of Arizona Cancer Center, Tucson, AZ, USA. · Moffitt Cancer Center, Tampa, FL, USA. · Oregon Health & Science University, Portland, OR, USA. · Stanford University Medical Center & VA Palo Alto Health Care System, Palo Alto, CA, USA. · Intermountain Healthcare & University of Utah, Salt Lake City, UT, USA. · University of Colorado, Aurora, CO, USA. · Columbia University, New York, NY, USA. · The Ohio State University, Columbus, OH, USA. · Harvard Medical School, Boston, MA, USA. · University of Pittsburgh, Pittsburgh, PA, USA. · Mayo Clinic Arizona, Scottsdale, AZ, USA. · University of California, Irvine, Orange, CA, USA. · University of Pennsylvania, Philadelphia, PA, USA. · The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Emory University & Atlanta VA Medical Center, Atlanta, GA, USA. · Northwestern University Feinberg School of Medicine, Chicago, IL USA. · Inova Medical Group, Fairfax, VA, USA. · St Luke's University Hospital & Temple University, Bethlehem, PA, USA. · Boston University, Boston, MA, USA. · Case Western Reserve University, Cleveland, OH, USA. · University of Missouri, Columbia, MO, USA. · Vanderbilt University, Nashville, TN, USA. · Harvard Medical School & Massachusetts General Hospital, Charlestown, MA, USA. · Winship Cancer Institute of Emory University, Atlanta, GA, USA. · The Christ Hospital, Cincinnati, OH, USA. · City of Hope National Cancer Center, Duarte, CA, USA. · Mayo Clinic Rochester, MN, USA. · Johns Hopkins University, Baltimore, MD. · NYU Langone Medical Center, New York, NY, USA. · Department of Dermatology, University of Athens, Andreas Sygros Hospital, Athens, Greece. · Bend Memorial Clinic, Bend, OR, USA. · University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Melanoma Manag · Pubmed #28758010.

ABSTRACT: Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

9 Review Operable Melanoma: Screening, Prognostication, and Adjuvant and Neoadjuvant Therapy. 2017

Tarhini, Ahmad A / Lorigan, Paul / Leachman, Sancy. ·From the University of Pittsburgh, Pittsburgh, PA; University of Manchester, Manchester, United Kingdom; Oregon Health & Science University, Portland, OR. ·Am Soc Clin Oncol Educ Book · Pubmed #28561661.

ABSTRACT: The importance of reducing the numbers of patients with late-stage melanoma, identifying which patients are most likely to progress, and treating these patients at the earliest possible stage cannot be overemphasized. Improved screening of patients prior to diagnosis has the advantage of identifying early-stage disease that is for the most part treatable by surgical methods. The process of melanoma screening is rapidly evolving through population-based programs, mobile health technologies, and advanced imaging tools. For patients with newly diagnosed melanoma, accurately estimating disease prognosis has important implications for management and follow-up. Prognostic factors are individual host- or tumor-related factors or molecules that correlate with genetic predisposition and clinical course. These include clinical covariates and host and tumor proteomic/genomic markers that allow the prognostic subclassification of patients. Adjuvant therapy for high-risk surgically resected melanoma targets residual micrometastatic disease with the goal of reducing the risk of relapse and mortality. In the United States, three regimens have achieved regulatory approval for adjuvant therapy, including high-dose interferon alpha, pegylated interferon alpha, and ipilimumab at 10 mg/kg. Phase III trials have reported benefits in relapse-free survival (all regimens) and overall survival (high-dose interferon alpha and ipilimumab). The management of locally/regionally advanced melanoma may benefit from neoadjuvant therapy, which is the subject of several ongoing studies. Recent studies have shown promising clinical activity and yielded important biomarker findings and mechanistic insights.

10 Review The use of immunotherapy in the treatment of melanoma. 2017

Achkar, Tala / Tarhini, Ahmad A. ·University of Pittsburgh, Pittsburgh, PA, USA. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Room 555, Pittsburgh, PA, 15232, USA. · University of Pittsburgh, Pittsburgh, PA, USA. tarhiniaa@upmc.edu. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Room 555, Pittsburgh, PA, 15232, USA. tarhiniaa@upmc.edu. ·J Hematol Oncol · Pubmed #28434398.

ABSTRACT: Patients with advanced melanoma have a compromised anti-tumor immune response leading to tumor immune tolerance and a tumor microenvironment conducive to disease progression. Immunotherapy that successfully overcomes this tumor-mediated immune suppression has made the greatest impact in the management of this disease over the past few years. This progress through immunotherapy builds upon earlier successes that interferon-α had in the treatment of melanoma in the adjuvant setting, as well as that of high-dose interleukin-2 in advanced melanoma. The development of immune checkpoint inhibitors has led to dramatic clinical activity in advanced melanoma. In particular, anti-CTLA4 and anti-PD1 monoclonal antibodies have taken us forward into the realm of longer survival and durable responses with the possibility of cure in a continuously increasing proportion of patients. Combination immunotherapeutic strategies and novel immunotherapeutic agents are being tested at an accelerated pace where the outlook for long-term survival benefits for the majority of patients appears brighter than ever.

11 Review Adjuvant Therapy for Melanoma. 2017

Agha, Aya / Tarhini, Ahmad A. ·University of Pittsburgh, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA. · University of Pittsburgh, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA. tarhiniaa@upmc.edu. · University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Room 555, Pittsburgh, PA, 15232, USA. tarhiniaa@upmc.edu. ·Curr Oncol Rep · Pubmed #28417343.

ABSTRACT: Systemic adjuvant therapy for surgically resected cutaneous melanoma that is at high risk for disease recurrence and death targets residual micrometastatic disease which is the source of future local or distant relapse. Interferon-alfa (IFNα) has been the most extensively studied in regimens that varied by dosage, route of administration, formulation, and duration of therapy. Most regimens have demonstrated improvements in relapse-free survival (RFS), while the regimen administered at high dosage (HDI) showed improvements in overall survival (OS) in two out of three RCTs. HDI benefits as measured by the hazard ratios (HR) in E1684 (vs. observation), E1690 (vs. observation), and E1694 (vs. vaccine) trials were estimated at 0.61, 0.78, and 0.67 (RFS) and 0.67, 1.0, and 0.72 (OS) when first reported with lesser estimates on later updates. Pegylated IFNα (peg-IFN) as studied in the European Organisation for Research and Treatment of Cancer (EORTC) 18991 trial in patients with stage III melanoma significantly reduced the risk of relapse (HR 0.87) with no impact on OS. More recently (EORTC 18071), ipilimumab at the high dose of 10 mg/kg was shown to significantly improve RFS (HR 0.76) and OS (HR 0.72) of stage III melanoma patients but at a significant cost in terms of immune-related toxicities. Ongoing adjuvant studies are testing ipilimumab at 3 or 10 mg/kg versus HDI (E1609) and the anti-PD-1 antibodies nivolumab (CheckMate 238) and pembrolizumab (KEYNOTE-054 and S1404).

12 Review Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. 2016

Boutros, Celine / Tarhini, Ahmad / Routier, Emilie / Lambotte, Olivier / Ladurie, Francois Leroy / Carbonnel, Franck / Izzeddine, Hassane / Marabelle, Aurelien / Champiat, Stephane / Berdelou, Armandine / Lanoy, Emilie / Texier, Matthieu / Libenciuc, Cristina / Eggermont, Alexander M M / Soria, Jean-Charles / Mateus, Christine / Robert, Caroline. ·Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. · University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA. · AP-HP, Internal Medicine Department, University Hospital of Bicêtre, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France. · Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France. · INSERM Unit U1184, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France. · Thoracic and Vascular Surgery Service, Centre Chirurgical Marie Lannelongue, 133 Avenue de la Resistance, 92350 Le Plessis-Robinson, France. · AP-HP, Department of Gastroenterology, University Hospital of Bicêtre, Paris Sud University, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France. · Department of Nephrology, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'hopital, 75013 Paris, France. · Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. · INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France. · Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. · Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. ·Nat Rev Clin Oncol · Pubmed #27141885.

ABSTRACT: Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.

13 Review Immunotherapy of Melanoma. 2016

Tarhini, Ahmad A. ·University of Pittsburgh Cancer Institute, 5150 Centre Avenue (555), Pittsburgh, PA 15232, USA. tarhiniaa@upmc.edu. ·Curr Mol Pharmacol · Pubmed #26177647.

ABSTRACT: The host antitumor immune response in patients with advanced melanoma is compromised with a bias towards tumor immune tolerance and a tumor microenvironment that facilitates disease survival and progression. Overcoming tumor-induced immune suppression has been one of the most significant advances in cancer therapy, making a cure an ever closer and achievable goal. Immunotherapeutic strategies in melanoma have been built upon the immunomodulatory qualities and the early successes of interferon-α in the melanoma adjuvant setting and interleukin-2 in the treatment of inoperable advanced melanoma. The recent advances in the field of immune checkpoint modulation and the unprecedented clinical activity in advanced melanoma opened the doors for novel agents and combinations that may potently overcome tumor tolerogenic mechanisms. Recent data with immune anti-CTLA4 and anti-PD1 monoclonal antibodies have moved the clinical management of advanced melanoma into a new era, an era of long-term survival and potential cures.

14 Review Neoadjuvant therapy for melanoma: a promising therapeutic approach and an ideal platform in drug development. 2015

Tarhini, Ahmad A. ·From the University of Pittsburgh School of Medicine and Cancer Institute, Pittsburgh, PA. ·Am Soc Clin Oncol Educ Book · Pubmed #25993220.

ABSTRACT: Patients with locoregionally advanced but surgically operable melanoma continue to carry a high risk of relapse and death despite the best available standard management approaches. Neoadjuvant studies targeting this patient population tested chemotherapy with temozolomide and biochemotherapy (BCT), in which BCT demonstrated high tumor response rates but was eventually abandoned with the failure of BCT to deliver survival benefits in randomized trials of metastatic disease. Smaller neoadjuvant immunotherapy studies with interferon (IFN) alfa and ipilimumab have yielded promising clinical activity and important mechanistic insights and biomarker findings. Newer targeted and immunotherapeutic agents and combinations currently are being translated into the neoadjuvant setting at an accelerated pace and carry significant clinical promise. In drug development, the neoadjuvant approach allows access to blood and tumor tissue before and after initiation of systemic therapy, which allows for the conduct of novel mechanistic and biomarker studies in the circulation and the tumor microenvironment. Such studies may guide drug development and allow for the discovery of predictive biomarkers selected on the basis of their capacity to classify patients according to the degree of benefit from treatment or the risk for significant toxicity.

15 Review Immune checkpoint blockade and interferon-α in melanoma. 2015

Rafique, Imran / Kirkwood, John M / Tarhini, Ahmad A. ·University of Pittsburgh Medical Center, Pittsburgh, PA. · University of Pittsburgh Medical Center, Pittsburgh, PA; University of Pittsburgh Cancer Institute, Pittsburgh, PA. · University of Pittsburgh Medical Center, Pittsburgh, PA; University of Pittsburgh Cancer Institute, Pittsburgh, PA. Electronic address: tarhiniaa@upmc.edu. ·Semin Oncol · Pubmed #25965362.

ABSTRACT: The quality of the host immune response in patients with advanced melanoma is compromised with a bias towards Th2-type polarization and a tumor microenvironment that facilitates disease progression. Overcoming tumor-induced immune suppression through strategies that build upon the immunomodulatory qualities and clinical activity of interferon-α as demonstrated in the melanoma adjuvant setting is a major clinical need. The recent advances in the field of immune checkpoint modulation and the unprecedented clinical activity in advanced melanoma opens the door on novel combinations that may overcome tumor tolerogenic mechanisms that are known to suppress the potent anti-tumor impact of interferon (IFN)-α. Promising preliminary data suggest that such combinations may move the clinical management of advanced melanoma into the next level, beyond what is currently seen with immune checkpoint blockers alone.

16 Review Intermediate-grade meningeal melanocytoma associated with nevus of Ota: a case report and review of the literature. 2015

Shin, Donghoon / Sinha, Milind / Kondziolka, Douglas S / Kirkwood, John M / Rao, Uma N M / Tarhini, Ahmad A. ·University of Pittsburgh, Pittsburgh, Pennsylvania, USA. ·Melanoma Res · Pubmed #25933209.

ABSTRACT: Meningeal melanocytomas are rare melanin-producing tumors that are often found to be benign. However, a small subset of these tumors can present as intermediate-grade melanocytomas (IGMs) that have histopathological features that are between those of benign melanocytomas and malignant melanomas. IGMs have the potential to recur and metastasize or progress to a more histologically high grade melanoma. Melanocytomas appear to differ from primary and metastatic melanoma by their prolonged clinical course and they appear to have different driver mutations (i.e. mutation of GNAQ gene). The association of a meningeal melanocytoma with nevus of Ota is extremely rare. To our knowledge, there have been only 10 reported cases of synchronous occurrence and only one of the cases involved an IGM. We report the second case of intermediate-grade meningeal melanocytoma that is associated with congenital nevus of Ota. Histopathological work-up confirmed the intermediate grade of the lesion and a driver GNAQ mutation was identified consistent with previous reports.

17 Review High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014. 2014

Dutcher, Janice P / Schwartzentruber, Douglas J / Kaufman, Howard L / Agarwala, Sanjiv S / Tarhini, Ahmad A / Lowder, James N / Atkins, Michael B. ·Associate Director, Cancer Research Foundation, Chappaqua, NY, USA. jpd4401@aol.com. · Associate Director of Clinical Operations, Professor of Surgery, IU Simon Cancer Center, 550 N University Blvd, Indianapolis, 46202, IN, USA. · Chief Surgical Officer and Associate Director for Clinical Science, Professor of Surgery, Rutgers Cancer Center Institute of New Jersey, 195 Little Albany Street, Room 2007, New Brunswick, 08901, NJ, USA. · Chief of Medical Oncology and Professor of Medicine, St. Luke's Cancer Center, Bethlehem, 18015, PA, USA. · Associate Professor of Medicine and Translational Science, University of Pittsburgh Cancer Institute, Suite 555, 5150 Centre Ave, Pittsburgh, 15232, PA, USA. · Senior Medical Director, Prometheus Laboratories Inc, 9410 Carroll Park Drive, San Diego, 92121, CA, USA. · Deputy Director, Professor of Medicine, Georgetown-Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd NW, NRB-E501, Washington, 20057, DC, USA. ·J Immunother Cancer · Pubmed #31546315.

ABSTRACT: Interleukin-2 (IL-2) was historically one of the few treatments for adults with stage IV solid tumors that could produce complete responses (CRs) that were often durable for decades without further therapy. The majority of complete responders with metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) could probably be classified as "cures". Recent publications have suggested improved efficacy, perhaps due to improved patient selection based on a better understanding of clinical features predicting outcomes. Guidelines for clinical management were established from experience at the National Cancer Institute (NCI) and an affiliation of institutions known as the Cytokine Working Group (CWG), who were among the first to utilize HD IL-2 treatment outside of the NCI. As new centers have opened, further management variations have emerged based upon center-specific experience, to optimize administration of IL-2 and provide high quality care for patients at each individual site. Twenty years of evolution in differing environments has led to a plethora of clinical experience and effective management approaches. The goal of this review is to summarize the spectrum of HD IL-2 treatment approaches, describing various effective strategies that incorporate newer adjunctive treatments for managing the side effects of IL-2 in patients with mRCC and mM. The goal for IL-2 therapy is typically to administer the maximum number of doses of IL-2 without putting the patient at unacceptable risk for severe, irreversible toxicity. This review is based upon a consensus meeting and includes guidelines on pre-treatment screening, criteria for administration and withholding doses, and defines consensus criteria for safe administration and toxicity management. The somewhat heterogeneous best practices of 2014 will be compared and contrasted with the guidelines provided in 2001 and the package inserts from 1992 and 1998.

18 Review Melanoma adjuvant therapy. 2014

Tarhini, Ahmad A / Thalanayar, Prashanth M. ·Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue (555), Pittsburgh, PA 15232, USA. Electronic address: tarhiniaa@upmc.edu. · Department of Internal Medicine, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA. ·Hematol Oncol Clin North Am · Pubmed #24880942.

ABSTRACT: Adjuvant therapy targets melanoma micrometastases in patients with surgically resected disease that carry a high risk of death from melanoma recurrence. In this setting, adjuvant therapy provides the greatest opportunity for cure before progression into advanced inoperable stages. In randomized clinical trials, interferon-alfa has been shown to have a significant impact on relapse-free survival and, at high dosage, on overall survival compared with observation (E1684) and the GMK vaccine (E1694). This article reviews melanoma adjuvant therapy along with the ongoing and planned clinical trials.

19 Review Advances in adjuvant therapy: potential for prognostic and predictive biomarkers. 2014

Davar, Diwakar / Tarhini, Ahmad A / Gogas, Helen / Kirkwood, John M. ·Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. ·Methods Mol Biol · Pubmed #24258973.

ABSTRACT: Melanoma is the third most common skin cancer but accounts for the majority of skin cancer-related mortality. The rapidly rising incidence and younger age at diagnosis has made melanoma a leading cause of lost productive years of life and has increased the urgency of finding improved adjuvant therapy for melanoma. Interferon-α was approved for the adjuvant treatment of resected high-risk melanoma following studies that demonstrated improvements in relapse-free survival and overall survival that were commenced nearly 30 years ago. The clinical benefits associated with this agent have been consistently observed across multiple studies and meta-analyses in terms of relapse rate, and to a smaller and less-consistent degree, mortality. However, significant toxicity and lack of prognostic and/or predictive biomarkers that would allow greater risk-benefit ratio have limited the more widespread adoption of this modality.Recent success with targeted agents directed against components of the MAP-kinase pathway and checkpoint inhibitors have transformed the treatment landscape in metastatic disease. Current research efforts are centered around discovering predictive/prognostic biomarkers and exploring the options for more effective regimens, either singly or in combination.

20 Review Adjuvant immunotherapy of melanoma and development of new approaches using the neoadjuvant approach. 2013

Davar, Diwakar / Tarhini, Ahmad A / Kirkwood, John M. ·Division of General Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. ·Clin Dermatol · Pubmed #23608443.

ABSTRACT: Melanoma is the third most common skin cancer but the leading cause of death from cutaneous malignancies. Although early-stage disease is frequently cured by surgical resection with excellent long-term survival, patients with deeper primary lesions (AJCC stage IIB-C) and those with microscopic (IIIA) or clinically evident regional lymph node or in-transit metastases (IIIB-C) have an increased risk of relapse and death, the latter approaching 70% or more at 5 years. In patients at high risk of recurrence/metastases, adjuvant therapy with high-dose interferon alpha-2b (HDI) following definitive surgical resection has been shown to improve relapse-free and overall survival. Neoadjuvant chemotherapy and/or radiotherapy have offered the prospect to improve regional recurrence risk and overall survival in several solid tumors. The advent of effective new molecularly targeted therapies for metastatic disease and new immunotherapies that overcome checkpoints of immune response have augmented the range of new options that are in current trial evaluation to determine their role as potential adjuvant therapies, alone and in combination with one another, and the established modality of IFN-α. The differential characteristics of the host immune response between early and advanced melanoma provide a strong mechanistic rationale for the use of neoadjuvant immunotherapeutic approaches in melanoma, and the opportunity to evaluate the mechanism of action suggest neoadjuvant trial evaluation for each of the new candidate agents and combinations of interest. Several neoadjuvant trials have been conducted in the phase II setting, which have illuminated the mechanism of IFN-α, as well as providing insight to the effects of anti-CTLA4 blocking antibodies. These agents (anti-CTLA4 blocking antibody ipilimumab, and BRAF inhibitor vemurafenib) are likely to be followed by other immunotherapies that may overcome the PD-1 checkpoint (anti-PD1 and anti-PDL-1) as well as other molecularly targeted agents such as the BRAF inhibitor dabrafenib and the MEK inhibitors trametinib, selumetinib, and MEK162 in the near future. Evaluation of the clinical role of these agents as adjuvant therapy will take years to accomplish to ascertain the relapse-free survival benefits and overall survival benefits of these agents, but neoadjuvant exploration may provide early critical evidence of the therapeutic benefits, as well as clarifying the mechanisms of these agents alone and in combination.

21 Review Tremelimumab: a review of development to date in solid tumors. 2013

Tarhini, Ahmad A. ·University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center Cancer Pavilion, 5150 Centre Avenue, Fifth Floor, Pittsburgh, PA 15232, USA. tarhiniaa@upmc.edu ·Immunotherapy · Pubmed #23444951.

ABSTRACT: Tremelimumab is an investigational, fully human IgG monoclonal antibody directed against CTLA-4, a coinhibitory receptor that represses effector T-cell activity in cancer. Tremelimumab has produced promising anticancer responses in early clinical trials. However, a phase III trial of tremelimumab monotherapy versus chemotherapy in advanced melanoma was stopped early when no statistically significant difference in overall survival was observed between the two interventions. This article describes tremelimumab's putative mechanism of action, its preclinical pharmacology and clinical results to date across a range of cancer settings as monotherapy, as well as in combination with other therapies. The failure of the Phase III trial in melanoma is examined and factors affecting the possible future clinical development of tremelimumab are also explored.

22 Review IFN-α in the treatment of melanoma. 2012

Tarhini, Ahmad A / Gogas, Helen / Kirkwood, John M. ·Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA. tarhiniaa@upmc.edu ·J Immunol · Pubmed #23042723.

ABSTRACT: Among the IFNs, IFN-α2 has been the most broadly evaluated clinically. At the molecular level, IFN-α has multiple effects in a variety of malignancies that range from antiangiogenic to potent immunoregulatory, differentiation-inducing, antiproliferative, and proapoptotic effects. A multitude of IFN-α2 regimens that may be classified as low dose, intermediate dose, and high dose have been evaluated as adjuvant therapy in melanoma. A durable impact on both relapse-free and overall survival was seen only with the regimen utilizing high-dose IFN-α2b tested in the Eastern Cooperative Oncology Group and intergroup trials E1684, E1690, and E1694 as adjuvant therapy for high-risk surgically resected melanoma (stage IIB or III). Adjuvant pegylated IFN-α2b has also been evaluated at maximally tolerable doses compared with the observation group in the European Organization for Research and Treatment of Cancer trial 18991 and has shown relapse-free survival benefits in patients with microscopic nodal disease.

23 Review Adjuvant therapy for melanoma. 2012

Davar, Diwakar / Tarhini, Ahmad A / Kirkwood, John M. ·Division of General Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA. ·Cancer J · Pubmed #22453021.

ABSTRACT: Estimates from the U.S. Surveillance, Epidemiology, and End Results registry suggest that melanoma incidence will reach 70,230 cases in 2011, of whom 8790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society.High-dose interferon-α-2b is the only agent approved for adjuvant therapy for melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However, toxicity affects compliance, and current research is focusing on biomarkers that may allow selection of patients with greater likelihood of response and exploring new agents either singly or in combination that may improve on the benefit of interferon.In this article, we review the data for the adjuvant therapy for malignant melanoma--focusing on the results obtained with various regimens testing the several formulations of interferon-α2 and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway.

24 Review Neoadjuvant therapy for high-risk bulky regional melanoma. 2011

Tarhini, Ahmad A / Pahuja, Shalu / Kirkwood, John M. ·Department of Medicine and Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. tarhiniaa@upmc.edu ·J Surg Oncol · Pubmed #21858833.

ABSTRACT: Clinically detectable regional lymph node melanoma metastasis (AJCC stage IIIB-C) carries a risk of relapse and death that approaches 70% at 5 years. Surgical management is the cornerstone of therapy, with postoperative adjuvant therapy utilizing high-dose interferon alfa-2b (HDI). Neoadjuvant chemotherapy or immunotherapy in addition to surgery has been demonstrated to improve outcome in the management of patients with a variety of solid tumors. In patients with melanoma, the characteristics of the host immune response differ between patients with earlier stage and those with more advanced stages of disease (and particularly between those with measurable active disease and those without measurable gross disease) providing rationale for neoadjuvant approaches with immunotherapy. Host immune tolerance is now understood to impede the results of therapy for advanced disease, but appears to be less an issue for patients with microscopic high-risk operable disease, where the host may be more susceptible to immunologic interventions. Phase II studies have shown that neoadjuvant biochemotherapy has limited activity in melanoma patients with local-regional metastases, where chemotherapy may potentially alter the effects of immunotherapeutic agents. Studies of neoadjuvant HDI therapy for high-risk melanoma patients with bulky regional stage IIIB-C lymphadenopathy have shown unexpectedly high clinical and pathologic response rates, without increased morbidity. Through the design of neoadjuvant trials utilizing promising emerging melanoma therapeutics in which it is possible to obtain biopsy samples before and after therapy, a greater understanding of the dynamic interaction between tumors and the immune system is possible. This should lead to the identification of new targets for the treatment of melanoma and aid the development of new immunotherapy that may have greater specificity and less toxicity. This will simplify the evaluation of promising new combinations of agents with HDI to build on the clinical, immunologic, and molecular effect of this therapy for patients with melanoma.

25 Review Cutaneous melanoma: a model to study cancer metastasis. 2011

Leong, Stanley P L / Gershenwald, Jeffrey E / Soong, Seng-Jaw / Schadendorf, Dirk / Tarhini, Ahmad A / Agarwala, Sanjiv / Hauschild, Axel / Soon, Christopher W M / Daud, Adil / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center and Research Institute, San Francisco, California 94115, USA. leongsx@cpmcri.org ·J Surg Oncol · Pubmed #21480247.

ABSTRACT: Nodal status in melanoma is a critically important prognostic factor for patient outcome. The survival rate drops to <10% when melanoma has spread beyond the regional lymph nodes and includes visceral involvement. In general, the process of melanoma metastasis is progressive in that dissemination of melanoma from the primary site to the regional lymph nodes occurs prior to systemic disease. The goal of this review article is to describe melanoma as a clinical model to study cancer metastasis. A future challenge is to develop a molecular taxonomy to subgroup melanoma patients at various stages of tumor progression for more accurate targeted treatment.

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