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Melanoma: HELP
Articles by Joseph I. Clark
Based on 15 articles published since 2008

Between 2008 and 2019, Joseph I. Clark wrote the following 15 articles about Melanoma.
+ Citations + Abstracts
1 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.

2 Clinical Trial Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the PROCLAIM 2017

Curti, Brendan / Daniels, Gregory A / McDermott, David F / Clark, Joseph I / Kaufman, Howard L / Logan, Theodore F / Singh, Jatinder / Kaur, Meenu / Luna, Theresa L / Gregory, Nancy / Morse, Michael A / Wong, Michael K K / Dutcher, Janice P. ·Providence Portland Medical Center, 4805 NE Glisan Street, Portland, OR, 97213, USA. · Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. · Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA. · Loyola University Medical Center, 2160 S First Avenue, Maywood, IL, 60153, USA. · Rutgers Cancer Center Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901, USA. · Indiana University Simon Cancer Center, 535 Barnhill Drive, Indianapolis, 46202, USA. · Primary Biostatistical Solutions, 2042 Carnarvon Ct, Victoria, BC, V8R2V3, Canada. · Prometheus Laboratories, 9410 Carroll Park Drive, San Diego, CA, 92121, USA. · Duke University Medical Center, 2301 Erwin Road, Durham, NC, 27705, USA. · MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Cancer Research Foundation of NY, 43 Longview Lane, Chappaqua, NY, 10514, USA. jpd4401@aol.com. ·J Immunother Cancer · Pubmed #29254506.

ABSTRACT: BACKGROUND: Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the PROCLAIM METHODS: Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. RESULTS: Median follow-up was 3.5+ years (range 1-8+ years), 152 irAEs were reported in 130 patients (8.4% of all PROCLAIM CONCLUSIONS: irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response.

3 Clinical Trial Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic melanoma. 2013

Gangadhar, Tara C / Clark, Joseph I / Karrison, Theodore / Gajewski, Thomas F. ·Department of Medicine, Section of Hematology/Oncology, The University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL, 60637, USA. ·Invest New Drugs · Pubmed #23151808.

ABSTRACT: BACKGROUND: Src kinases are activated in melanoma, and inhibition of Src kinase activity has pre-clinical anti-tumor effects. Targeting this pathway could therefore have therapeutic activity in patients with metastatic melanoma. PATIENTS AND METHODS: We conducted a multi-center, open-label study of the Src kinase inhibitor saracatanib (AZD0530) in patients with metastatic melanoma. Twenty-three patients received saracatanib at a dose of 175 mg daily. The primary objectives were to determine whether this agent had clinical activity in patients with advanced melanoma and whether it increased progression free survival. Functional effects on circulating T cells were also assessed. RESULTS: Twenty-three patients received oral saracatanib on a continuous daily dosing regimen. There were no objective clinical responses. Saracatanib was generally well tolerated with few grade 3-4 adverse events. T cell function was inhibited in most patients, based on decreased superantigen-induced IL-2 production in post- versus pre-treatment samples. CONCLUSIONS: Saracatanib has minimal clinical activity as a single agent in an unselected population of patients with advanced melanoma, as evidenced by a lack of objective responses in this study. Reduced T cell cytokine production in most treated patients suggests potential immune suppressive activity by this agent.

4 Clinical Trial Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. 2012

Margolin, Kim / Ernstoff, Marc S / Hamid, Omid / Lawrence, Donald / McDermott, David / Puzanov, Igor / Wolchok, Jedd D / Clark, Joseph I / Sznol, Mario / Logan, Theodore F / Richards, Jon / Michener, Tracy / Balogh, Agnes / Heller, Kevin N / Hodi, F Stephen. ·University of Washington, Seattle, WA 98109, USA. kmargoli@seattlecca.org ·Lancet Oncol · Pubmed #22456429.

ABSTRACT: BACKGROUND: Brain metastases commonly develop in patients with melanoma and are a frequent cause of death of patients with this disease. Ipilimumab improves survival in patients with advanced melanoma. We aimed to investigate the safety and activity of this drug specifically in patients with brain metastases. METHODS: Between July 31, 2008, and June 3, 2009, we enrolled patients with melanoma and brain metastases from ten US centres who were older than 16 years into two parallel cohorts. Patients in cohort A were neurologically asymptomatic and were not receiving corticosteroid treatment at study entry; those in cohort B were symptomatic and on a stable dose of corticosteroids. Patients were to receive four doses of 10 mg/kg intravenous ipilimumab, one every 3 weeks. Individuals who were clinically stable at week 24 were eligible to receive 10 mg/kg intravenous ipilimumab every 12 weeks. The primary endpoint was the proportion of patients with disease control, defined as complete response, partial response, or stable disease after 12 weeks, assessed with modified WHO criteria. Analyses of safety and efficacy included all treated patients. This trial is registered with ClinicalTrials.gov, number NCT00623766. FINDINGS: We enrolled 72 patients: 51 into cohort A and 21 into cohort B. After 12 weeks, nine patients in cohort A exhibited disease control (18%, 95% CI 8-31), as did one patient in cohort B (5%, 0·1-24). When the brain alone was assessed, 12 patients in cohort A (24%, 13-38) and two in cohort B (10%, 1-30) achieved disease control. We noted disease control outside of the brain in 14 patients (27%, 16-42) in cohort A and in one individual (5%, 0·1-24) in cohort B. The most common grade 3 adverse events in cohort A were diarrhoea (six patients [12%]) and fatigue (six [12%]); in cohort B, they were dehydration (two individuals [10%]), hyperglycaemia (two [10%]), and increased concentrations of serum aspartate aminotransferase (two [10%]). One patient in each cohort had grade 4 confusion. The most common grade 3 immune-related adverse events were diarrhoea (six patients [12%]) and rash (one [2%]) in cohort A, and rash (one individual [5%]) and increased concentrations of serum aspartate aminotransferase (two [10%]) in cohort B. One patient in cohort A died of drug-related complications of immune-related colitis. INTERPRETATION: Ipilimumab has activity in some patients with advanced melanoma and brain metastases, particularly when metastases are small and asymptomatic. The drug has no unexpected toxic effects in this population. FUNDING: Bristol-Myers Squibb.

5 Clinical Trial Improved survival with ipilimumab in patients with metastatic melanoma. 2010

Hodi, F Stephen / O'Day, Steven J / McDermott, David F / Weber, Robert W / Sosman, Jeffrey A / Haanen, John B / Gonzalez, Rene / Robert, Caroline / Schadendorf, Dirk / Hassel, Jessica C / Akerley, Wallace / van den Eertwegh, Alfons J M / Lutzky, Jose / Lorigan, Paul / Vaubel, Julia M / Linette, Gerald P / Hogg, David / Ottensmeier, Christian H / Lebbé, Celeste / Peschel, Christian / Quirt, Ian / Clark, Joseph I / Wolchok, Jedd D / Weber, Jeffrey S / Tian, Jason / Yellin, Michael J / Nichol, Geoffrey M / Hoos, Axel / Urba, Walter J. ·Dana-Farber Cancer Institute, Boston, MA 02115, USA. stephen_hodi@dfci.harvard.edu ·N Engl J Med · Pubmed #20525992.

ABSTRACT: BACKGROUND: An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. METHODS: A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. RESULTS: The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. CONCLUSIONS: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

6 Clinical Trial Cytokine working group study of lymphodepleting chemotherapy, interleukin-2, and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma: clinical outcomes and peripheral-blood cell recovery. 2010

Gunturu, Krishna S / Meehan, Kenneth R / Mackenzie, Todd A / Crocenzi, Todd S / McDermott, David / Usherwood, Edward J / Margolin, Kim A / Crosby, Nancy A / Atkins, Michael B / Turk, Mary Jo / Ahonen, Cory / Fuse, Shinichiro / Clark, Joseph I / Fisher, Jan L / Noelle, Randolph J / Ernstoff, Marc S. ·Section of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03756, USA. ·J Clin Oncol · Pubmed #20124177.

ABSTRACT: PURPOSE: Recovery of lymphocyte populations after lymphocyte depletion is implicated in therapeutic immune pathways in animal models and in patients with cancer. We sought to evaluate the effects of chemotherapy-induced lymphodepletion followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) and high-dose interleukin-2 (IL-2) therapy on clinical response and the recovery of lymphocyte subcompartments in patients with metastatic melanoma. PATIENTS AND METHODS: This was a two-stage phase II trial design. Patients with measurable metastatic melanoma were treated with intravenous cyclophosphamide (60 mg/kg, days 1 and 2) and fludarabine (25 mg/m(2), day 3 through 7) followed by two 5-day courses of intravenous high-dose bolus IL-2 (600,000 U/kg; days 8 through 12 and 21 through 25). GM-CSF (250 microg/m(2)/d beginning day 8) was given until granulocyte recovery. Lymphocyte recovery profiles were determined by flow cytometric phenotyping at regular intervals, and clinical outcome was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: The trial was stopped at the end of stage 1 with four of 18 objective responses noted. Twelve patients had detailed lymphocyte subcompartments evaluated. After lymphodepletion, we observed an induction of regulatory cells (CD4+ T regulatory cells; CD8+ T suppressor cells) and of T memory cells (CD8+ T central memory cells; T effector memory RA+ cells). Expansion of circulating melanoma-specific CD8(+) cells was observed in one of four HLA-A2-positive patients. CONCLUSION: Chemotherapy-induced lymphodepletion modulates the homeostatic repopulation of the lymphocyte compartment and influences recovering lymphocyte subpopulations. Clinical activity seems similar to standard high-dose aldesleukin alone.

7 Clinical Trial Phase 2 trial of combination thalidomide plus temozolomide in patients with metastatic malignant melanoma: Southwest Oncology Group S0508. 2010

Clark, Joseph I / Moon, James / Hutchins, Laura F / Sosman, Jeffrey A / Kast, W Martin / Da Silva, Diane M / Liu, P Y / Thompson, John A / Flaherty, Lawrence E / Sondak, Vernon K. ·Cardinal Bernardin Cancer Center, Loyola University Medical Center, Division of Hematology/Oncology, 2160 South First Avenue, Maywood, IL 60153, USA. jclark@lumc.edu ·Cancer · Pubmed #19918923.

ABSTRACT: BACKGROUND: In limited institution phase 2 studies, thalidomide and temozolomide has yielded response rates (RRs) up to 32% for advanced melanoma, leading to the use of this combination as "standard" by some. We conducted a multicenter phase 2 trial to better define the clinical efficacy of thalidomide and temozolomide and the immune modulatory effects of thalidomide, when combined with temozolomide, in patients with metastatic melanoma. METHODS: Patients must have had stage IV cutaneous melanoma, no active brain metastases, Zubrod PS 0-1, up to 1 prior systemic therapy excluding thalidomide, temozolomide, or dacarbazine, adequate organ function, and given informed consent. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), RR, toxicities, and assessment of relationships between biomarkers and clinical outcomes. Patients received thalidomide (200 mg/d escalated to 400 mg/d for patients <70, or 100 mg/d escalated to 250 mg/d for patients > or =70) plus temozolomide (75 mg/m(2)/d x 6 weeks, and then 2 weeks rest). RESULTS: Sixty-four patients were enrolled; 2 refused treatment. The 6-month PFS was 15% (95% confidence interval [CI], 6%-23%), the 1-year OS was 35% (95% CI, 24%-47%), and the RR was 13% (95% CI, 5%-25%), all partial. One treatment-related death occurred from myocardial infarction; 3 other grade 4 events occurred, including pulmonary embolism, neutropenia, and central nervous system (CNS) ischemia. There was no significant correlation between biomarkers and PFS or OS. CONCLUSIONS: This combination of thalidomide and temozolomide does not appear to have a clinical benefit that exceeds dacarbazine alone. We would not recommend it further for phase 3 trials or for standard community use.

8 Clinical Trial A phase II study of oxaliplatin, docetaxel, and GM-CSF in patients with previously treated advanced melanoma. 2010

Locke, Frederick / Clark, Joseph I / Gajewski, Thomas F. ·Department of Medicine, University of Chicago, Chicago, IL 60637, USA. ·Cancer Chemother Pharmacol · Pubmed #19597729.

ABSTRACT: PURPOSE: Although much focus has been placed on immunotherapy for melanoma, further development of chemotherapy approaches is needed. Melanoma is responsive to platinum compounds and taxanes, but there is limited experience with combinations of these agents. Oxaliplatin has been reported to have detectable activity in melanoma, and a phase I study has identified a tolerable dose and schedule of oxaliplatin in combination with docetaxel and hematopoietic growth factor support. GM-CSF has a theoretical advantage of immune potentiation. These considerations supported the study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma. METHODS: Eligibility included adequate organ function, PSThis combination of oxaliplatin, docetaxel, and GM-CSF has limited clinical activity in previously treated patients with advanced melanoma. Exploration in treatment-naïve patients may still be warranted.

9 Clinical Trial Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study. 2008

Atkins, Michael B / Sosman, Jeffrey A / Agarwala, Sanjiv / Logan, Theodore / Clark, Joseph I / Ernstoff, Marc S / Lawson, David / Dutcher, Janice P / Weiss, Geoffrey / Curti, Brendan / Margolin, Kim A. ·Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. Matkins@bidmc.harvard.edu ·Cancer · Pubmed #18792064.

ABSTRACT: BACKGROUND: The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS: Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m(2)/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS: Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS: The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population.

10 Clinical Trial Three phase II cytokine working group trials of gp100 (210M) peptide plus high-dose interleukin-2 in patients with HLA-A2-positive advanced melanoma. 2008

Sosman, Jeffrey A / Carrillo, Carole / Urba, Walter J / Flaherty, Lawrence / Atkins, Michael B / Clark, Joseph I / Dutcher, Janet / Margolin, Kim A / Mier, James / Gollob, Jarod / Kirkwood, John M / Panka, David J / Crosby, Nancy A / O'Boyle, Kevin / LaFleur, Bonnie / Ernstoff, Marc S. ·Vanderbilt-Ingram Cancer Center Vanderbilt, University Medical Center, Section of Hematology/Oncology, 777 Preston Research Bldg, Nashville, TN 37232-6307, USA. jeff.sosman@vanderbilt.edu ·J Clin Oncol · Pubmed #18467720.

ABSTRACT: PURPOSE: High-dose interleukin-2 (IL-2) induces responses in 15% to 20% of patients with advanced melanoma; 5% to 8% are durable complete responses (CRs). The HLA-A2-restricted, modified gp100 peptide (210M) induces T-cell immunity in vivo and has little antitumor activity but, combined with high-dose IL-2, reportedly has a 42% (13 of 31 patients) response rate (RR). We evaluated 210M with one of three different IL-2 schedules to determine whether a basis exists for a phase III trial. PATIENTS AND METHODS: In three separate phase II trials, patients with melanoma received 210M subcutaneously during weeks 1, 4, 7, and 10 and standard high-dose IL-2 during weeks 1 and 3 (trial 1), weeks 7 and 9 (trial 2), or weeks 1, 4, 7, and 10 (trial 3). Immune assays were performed on peripheral-blood mononuclear cells collected before and after treatment. RESULTS: From 1998 to 2003, 131 patients with HLA-A2-positive were enrolled. With 60-month median follow-up time, the overall RR for 121 assessable patients was 16.5% (95% CI, 10% to 26%); the RRs were 23.8% in trial 1 (42 patients), 12.5% in trial 2 (40 patients), and 12.8% in trial 3 (39 patients). There were 11 CRs (9%) and nine partial responses (7%), with 11 patients (9%) progression free at >or= 30 months. Immune studies including assays of CD3-zeta expression and numbers of CD4(+)/CD25(+)/FoxP3(+) regulatory T cells, CD15(+)/CD11b(+)/CD14(-) immature myeloid-derived cells, and CD8(+)gp100 tetramer-positive cells in the blood did not correlate with clinical benefit. CONCLUSION: The results again demonstrate efficacy of high-dose IL-2 in advanced melanoma but did not demonstrate the promising clinical activity reported with vaccine and high-dose IL-2 in any of three phase II trials.

11 Article Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells. 2018

Moore, Tamson / Wagner, Courtney Regan / Scurti, Gina M / Hutchens, Kelli A / Godellas, Constantine / Clark, Ann Lau / Kolawole, Elizabeth Motunrayo / Hellman, Lance M / Singh, Nishant K / Huyke, Fernando A / Wang, Siao-Yi / Calabrese, Kelly M / Embree, Heather D / Orentas, Rimas / Shirai, Keisuke / Dellacecca, Emilia / Garrett-Mayer, Elizabeth / Li, Mingli / Eby, Jonathan M / Stiff, Patrick J / Evavold, Brian D / Baker, Brian M / Le Poole, I Caroline / Dropulic, Boro / Clark, Joseph I / Nishimura, Michael I. ·Department of Surgery, Loyola University Chicago, 2160 S. 1st Avenue, Maywood, IL, 60153, USA. tamoore@luc.edu. · Department of Medicine, Loyola University Chicago, 2160 S. 1st Avenue, Maywood, IL, 60153, USA. · Department of Surgery, Loyola University Chicago, 2160 S. 1st Avenue, Maywood, IL, 60153, USA. · Department of Pathology, Loyola University Chicago, 2160 S. 1st Avenue, Maywood, IL, 60153, USA. · Forefront Dermatology, 801 York St, Manitowoc, WI, 54220, USA. · O. Wayne Rollins Research Center, Emory University, Room 3127, 1510 Clifton Road NE, Atlanta, GA, 30322, USA. · Department of Chemistry & Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN, 46656, USA. · Abbvie, 1 North Waukegan Road, North Chicago, IL, 60064, USA. · Lentigen Technology Inc, A Miltenyi Biotec Company, 910 Clopper Road Suite 200S, Gaithersburg, MD, 20878, USA. · Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Charleston, SC, 29425, USA. · Dartmouth-Hitchcock, Norris Cotton Cancer Center, One Medical Center Dr, Lebanon, NH, 03756, USA. · Department of Microbiology, and Immunology, Loyola University Chicago, 2160 S. 1st Avenue, Maywood, IL, USA. · Bluebird Biology, 60 Binney St., Cambridge, MA, 02142, USA. · Lurie Comprehensive Cancer Center, Department of Dermatology, Northwestern University at Chicago, Room 5-113, 303 East Superior Street, Chicago, IL, 60611, USA. ·Cancer Immunol Immunother · Pubmed #29052782.

ABSTRACT: Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4

12 Article Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma. 2016

Alva, Ajjai / Daniels, Gregory A / Wong, Michael K K / Kaufman, Howard L / Morse, Michael A / McDermott, David F / Clark, Joseph I / Agarwala, Sanjiv S / Miletello, Gerald / Logan, Theodore F / Hauke, Ralph J / Curti, Brendan / Kirkwood, John M / Gonzalez, Rene / Amin, Asim / Fishman, Mayer / Agarwal, Neeraj / Lowder, James N / Hua, Hong / Aung, Sandra / Dutcher, Janice P. ·University of Michigan, Ann Arbor, MI, USA. · Moores Cancer Center, University of California San Diego, La Jolla, CA, USA. · University of Southern California, Los Angeles, CA, USA. · M.D. Anderson Cancer Center, Houston, TX, USA. · Rutgers Cancer Center Institute of New Jersey, New Brunswick, NJ, USA. · Duke University Medical Center, Durham, NC, USA. · Beth Israel Deaconess Medical Center, Boston, MA, USA. · Loyola University Medical Center, Maywood, IL, USA. · St. Luke's University Health Network and Temple University, Bethlehem, PA, USA. · Hematology/Oncology Clinic, Baton Rouge, LA, USA. · Indiana University Simon Cancer Center, Indianapolis, IN, USA. · Nebraska Cancer Specialists, Omaha, NE, USA. · Providence Portland Medical Center, Portland, OR, USA. · Hillman Cancer Center Research, University of Pittsburgh Cancer Institute, Pavillion L1 32c, Pittsburgh, PA, USA. · University of Colorado Cancer Center, Aurora, CO, USA. · Levine Cancer Institute, Charlotte, NC, USA. · Moffitt Cancer Center, Tampa, FL, USA. · Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. · Astex Pharmaceuticals, Pleasanton, CA, USA. · Prometheus Laboratories Inc., San Diego, CA, USA. · Nektar Therapeutics, San Francisco, CA, USA. · Cancer Research Foundation, Chappaqua, NY, USA. jpd4401@aol.com. ·Cancer Immunol Immunother · Pubmed #27714434.

ABSTRACT: High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIM

13 Article Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma. 2016

Klarquist, Jared / Tobin, Kristen / Farhangi Oskuei, Peyman / Henning, Steven W / Fernandez, Manuel F / Dellacecca, Emilia R / Navarro, Flor C / Eby, Jonathan M / Chatterjee, Shilpak / Mehrotra, Shikhar / Clark, Joseph I / Le Poole, I Caroline. ·Oncology Research Institute, Loyola University Chicago, Maywood, Illinois. · Department of Medicine, Loyola University Chicago, Maywood, Illinois. · Department of Surgery/Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina. · Oncology Research Institute, Loyola University Chicago, Maywood, Illinois. ilepool@luc.edu. · Departments of Pathology, Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois. ·Cancer Res · Pubmed #27634754.

ABSTRACT: T regulatory cells (Treg) avert autoimmunity, but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation in melanoma, we evaluated chemokine expression in patients. A 5-fold increase was documented in the Treg chemoattractants CCL22 and CCL1 in melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3

14 Article Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders. 2016

Johnson, Douglas B / Sullivan, Ryan J / Ott, Patrick A / Carlino, Matteo S / Khushalani, Nikhil I / Ye, Fei / Guminski, Alexander / Puzanov, Igor / Lawrence, Donald P / Buchbinder, Elizabeth I / Mudigonda, Tejaswi / Spencer, Kristen / Bender, Carolin / Lee, Jenny / Kaufman, Howard L / Menzies, Alexander M / Hassel, Jessica C / Mehnert, Janice M / Sosman, Jeffrey A / Long, Georgina V / Clark, Joseph I. ·Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. · Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. · Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia5Department of Medicine, University of Sydney, Sydney, New South Wales, Australia. · Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York. · Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee. · Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia. · medical student at School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. · Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick. · Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany. · Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia. · Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick. · Department of Medicine, Loyola University Medical Center, Maywood, Illinois. ·JAMA Oncol · Pubmed #26633184.

ABSTRACT: IMPORTANCE: Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known. OBJECTIVE: To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015. EXPOSURE: Ipilimumab therapy. MAIN OUTCOMES AND MEASURES: Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively. RESULTS: Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.

15 Article Evolving treatment strategies in thin cutaneous head and neck melanoma: 1 institution's experience. 2011

Jaber, James J / Clark, Joseph I / Muzaffar, Kamil / Ruggiero, Francis P / Feustel, Paul J / Frett, Michael J / Zender, Chad A. ·Department of Otolaryngology-Head and Neck Surgery, Loyola University Medical Center, Maywood, Illinois, USA. ·Head Neck · Pubmed #20848424.

ABSTRACT: BACKGROUND: Although existing melanoma literature provides recommendations for thinner lesions (≤1 mm) within a heterogeneous population, a focus on the head and neck group is less pervasive. METHODS: The records of 49 node-negative individuals with thin head and neck melanoma that underwent surgical intervention ± sentinel lymph node (SLN) biopsy were reviewed. RESULTS: A significant increased Breslow thickness and mitotic rate, and a trend toward significance in Clark level ≥ IV were shown in patients that underwent an SLN biopsy versus those that did not. The total number of positive biopsies was 2 (5%). In our subset analysis using the modified American Joint Committee on Cancer recommendations by Wong and colleagues, the incidence of positive SLN biopsy would have increased to 11%. CONCLUSION: We advocate performing an SLN biopsy in thin head and neck melanomas for primary tumors > 0.75 mm, regardless of "high-risk" features as described by Wong and colleagues.