JITC Digest December 2016


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Inside this Issue:


Letter from the Editor

pedro-romero_1__1_.jpgDear JITC Readers:

Following a momentous year for advances in cancer immunotherapy, the Journal for ImmunoTherapy of Cancer (JITC) is pleased to highlight a rich variety of papers in this issue, including two new clinical guidelines from SITC’s Cancer Immunotherapy Guidelines Task Forces. These evidence-based consensus recommendations for the clinical application of immunotherapy focus on the treatment of hematologic malignancies and prostate carcinoma.

“The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia" provides recommendations for the clinical application of immunotherapy for the three named hematologic malignancies. Recommendations focus on issues related to patient selection, toxicity management, clinical endpoints and the sequencing or combination of therapies. Organized by disease type, each section of the paper provides recommendations on current treatments, highlights emerging immunotherapies and addresses issues related to immunotherapy research as they pertain to each particular disease setting.

"The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma" focuses on sipuleucel-T, the first and currently only immunotherapy agent approved for prostate cancer. This consensus statement, generated by a panel of leading experts, examines this autologous dendritic cell vaccine through discussion of issues related to patient selection, patient monitoring during and after treatment and sequencing or combination with other treatments. The manuscript also identifies emerging immunotherapies that are in late-stage clinical trials, such as vaccines and immune modulators.

With best regards,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer


Case Report

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Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy

Jared R. Lowe, Daniel J. Perry, April K. S. Salama, Clayton E. Mathews, Larry G. Moss and Brent A. Hanks
Journal for ImmunoTherapy of Cancer 2016, 4:89 (20 December 2016)

From the Authors

"The ability to predict the development of toxicities to checkpoint inhibitors represents a clinically meaningful goal in the field of cancer immunotherapy. We describe a genetic risk assessment based on HLA alleles and single nucleotide polymorphisms of a patient following the development of fulminant autoimmune type I diabetes while undergoing combination ipilimumab/nivolumab immunotherapy."

Brent A. Hanks, MD, PhD — Duke University Medical Center

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Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report & review of the literature

Joshua E. Reuss, Paul R. Kunk, Anne M. Stowman, Alejandro A. Gru, Craig L. Slingluff Jr. and Elizabeth M. Gaughan
Journal for ImmunoTherapy of Cancer 2016, 4:94 (20 December 2016)

From the Authors

"With the routine use of combination and sequential checkpoint inhibitor therapy, providers are challenged to interpret and manage varied responses. Tissue biopsy of new lesions developing while a patient is receiving immunotherapy is an important step to help guide decision making, as non-melanoma lesions can mimic disease progression."

Elizabeth M. Gaughan, MD — University of Virginia


Commentary

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Being “penny-wise but pound foolish” in cancer immunotherapy research: the urgent need for mouse cancer models to reflect human modifying factors

William J. Murphy
Journal for ImmunoTherapy of Cancer 2016, 4:88 (20 December 2016)

From the Author

"Immunotherapy is increasingly applied as a mainstream cancer regimen yet its strength – the ability to amplify and sustain responses – can also be a drawback with regard to off-target effects. There is a critical need to develop and use preclinical models that better emulate human immune status in cancer."

William J. Murphy, PhD — University of California, Davis

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Advances in immunotherapeutic strategies for colorectal cancer commentary on: tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients by Halama et al

Dustin A. Deming
Journal for ImmunoTherapy of Cancer 2016, 4:93 (20 December 2016)

From the Author

"Here we provide commentary on a manuscript from Halama et al. examining CCL5/CCR5 as an immune biomarker and the potential role of anti-CCR5 agents for the treatment of patients with colorectal cancer."

Excerpt from Article Abstract

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A quantum leap in cancer vaccines?

Eli Gilboa
Journal for ImmunoTherapy of Cancer 2016, 4:87 (20 December 2016)

From the Author

"In a recent article in Nature, Kranz and colleagues describe what appears to be a remarkably effective and relatively simple approach, using tumor antigen-encoding mRNA complexed to cationic lipid carriers, RNA-lipoplexes. Amazingly, all it took was to tweak the net charge of the RNA to lipid ratio to be slightly negative."

Eli Gilboa, PhD — University of Miami


Position Article & Guidelines

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The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma

Douglas G. McNeel, Neil H. Bander, Tomasz M. Beer, Charles G. Drake, Lawrence Fong, Stacey Harrelson, Philip W. Kantoff, Ravi A. Madan, William K. Oh, David J. Peace, Daniel P. Petrylak, Hank Porterfield, Oliver Sartor, Neal D. Shore, Susan F. Slovin, Mark N. Stein, Johannes Vieweg and James L. Gulley
Journal for ImmunoTherapy of Cancer 2016, 4:92 (20 December 2016)

From the Authors

"These consensus guidelines provide guidance for the use of sipuleucel-T, currently the only approved immunotherapy in prostate cancer, and lay the groundwork for the development and subsequent clinical implementation of novel immune-based agents currently being explored in prostate cancer. We look forward to updating these guidelines as new immunotherapy agents are approved for patients with prostate cancer."

James L. Gulley, MD, PhD, FACP — National Cancer Institute

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The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia

Michael Boyiadzis, Michael R. Bishop, Rafat Abonour, Kenneth C. Anderson, Stephen M. Ansell, David Avigan, Lisa Barbarotta, Austin John Barrett, Koen Van Besien, P. Leif Bergsagel, Ivan Borrello, Joshua Brody, Jill Brufsky, Mitchell Cairo, Ajai Chari, Adam Cohen, Jorge Cortes, Stephen J. Forman, Jonathan W. Friedberg, Ephraim J. Fuchs, Steven D. Gore, Sundar Jagannath, Brad S. Kahl, Justin Kline, James N. Kochenderfer, Larry W. Kwak, Ronald Levy, Marcos de Lima, Mark R. Litzow, Anuj Mahindra, Jeffrey Miller, Nikhil C. Munshi, Robert Z. Orlowski, John M. Pagel, David L. Porter, Stephen J. Russell, Karl Schwartz, Margaret A. Shipp, David Siegel, Richard M. Stone, Martin S. Tallman, John M. Timmerman, Frits Van Rhee, Edmund K. Waller, Ann Welsh, Michael Werner, Peter H. Wiernik and Madhav V. Dhodapkar
Journal for ImmunoTherapy of Cancer 2016, 4:90 (20 December 2016)

From the Authors

"This document provides the first consensus opinion on the application of current and emerging immune-based approaches in the management of hematologic malignancies. SITC should be congratulated for engaging clinical and research leaders in this field, as well as patient and nursing advocates and SITC membership for generating this important evidence-based document."

Madhav Dhodapkar, MD — Yale University


Research Article

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Fusion of the dendritic cell-targeting chemokine MIP3α to melanoma antigen Gp100 in a therapeutic DNA vaccine significantly enhances immunogenicity and survival in a mouse melanoma model

James T. Gordy, Kun Luo, Hong Zhang, Arya Biragyn and Richard B. Markham
Journal for ImmunoTherapy of Cancer 2016, 4:96 (20 December 2016)

From the Authors

"Although therapeutic cancer vaccines have been mostly disappointing in the clinic, the advent of novel immunotherapies and the future promise of neoantigen-based therapies have created the need for new vaccine modalities that can easily adapt to current and future developments in cancer immunotherapy."

Excerpt from Article Abstract

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Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small cell lung cancer patients

Mizuki Nishino, Nikhil H. Ramaiya, Emily S. Chambers, Anika E. Adeni, Hiroto Hatabu, Pasi A. Jänne, F. Stephen Hodi and Mark M. Awad
Journal for ImmunoTherapy of Cancer 2016, 4:84 (20 December 2016)

From the Authors

"Immune-related response evaluations using irRECIST1.1 in advanced non-small cell lung cancer patients treated with nivolumab resulted in the identical response rate to the conventional RECIST1.1, with no pseudoprogression cases during the study. Adrenal lesions and lymph nodes were more responsive and liver lesions were less responsive to nivolumab, indicating the impact of tumor microenvironments in different organs on immune-related tumor response."

Mizuki Nishino, MD, MPH — Dana-Farber Cancer Institute

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A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma

Andrew S. Brohl, Nikhil I. Khushalani, Zeynep Eroglu, Joseph Markowitz, Ram Thapa, Y. Ann Chen, Ragini Kudchadkar and Jeffrey S. Weber
Journal for ImmunoTherapy of Cancer 2016, 4:85 (20 December 2016)

From the Authors

"In our 31 patient study, we report the feasibility of treatment with the combination of ipilimumab and peginterferon alfa-2b in the setting of advanced melanoma. A promising efficacy signal was observed, with 40% of patients experiencing an objective response to treatment."

Andrew S. Brohl, MD — H. Lee Moffitt Cancer Center


Review

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A New VISTA on combination therapy for negative checkpoint regulator blockade

Jie Deng, Isabelle Le Mercier, Anna Kuta and Randolph J. Noelle
Journal for ImmunoTherapy of Cancer 2016, 4:86 (20 December 2016)

From the Authors

"As combination immunotherapy continues to rise to the forefront of cancer treatment, we discuss how the strategic combination of current established NCR with anti-VISTA antibody can be used to target non-redundant pathways."

Isabelle Le Mercier, PhD — ImmuNext, Inc.

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Challenges and opportunities for checkpoint blockade in T cell lymphoproliferative disorders

Tycel Phillips, Sumana Devata and Ryan A. Wilcox
Journal for ImmunoTherapy of Cancer 2016, 4:95 (20 December 2016)

From the Authors

"The results achieved thus far with checkpoint blockade in T cell lymphomas, while encouraging, suggest that novel combination strategies will be needed to achieve durable remissions in patients afflicted with these aggressive non-Hodgkin lymphomas."

Ryan A. Wilcox, MD, PhD — University of Michigan

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Canine cancer immunotherapy studies: linking mouse and human

Jiwon S. Park, Sita S. Withers, Jaime F. Modiano, Michael S. Kent, Mingyi Chen, Jesus I. Luna, William T. N. Culp, Ellen E. Sparger, Robert B. Rebhun, Arta M. Monjazeb, William J. Murphy and Robert J. Canter
Journal for ImmunoTherapy of Cancer 2016, 4:97 (20 December 2016)

From the Authors

"There is a growing body of evidence that spontaneous cancers in dogs represent attractive translational models that bridge mechanistic studies in mice to the heterogeneous human situation where clinical trials are time and resource intensive and may deliver ambiguous results. Particularly in the burgeoning field of immunotherapy, dogs offer an innovative model for translational research, as they present many of the same challenges faced in “scaling up” a therapeutic system dependent on complex interactions between multiple cell types, while simultaneously allowing for long-term assessment of efficacy and toxicities."

Robert Canter, MD, MAS, FACS — University of California Davis Health System


November Highly Accessed Articles

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Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma

Brian I. Rini, David F. McDermott, Hans Hammers, William Bro, Ronald M. Bukowski, Bernard Faba, Jo Faba, Robert A. Figlin, Thomas Hutson, Eric Jonasch, Richard W. Joseph, Bradley C. Leibovich, Thomas Olencki, Allan J. Pantuck, David I. Quinn, Virginia Seery, Martin H. Voss, Christopher G. Wood, Laura S. Wood and Michael B. Atkins
Journal for ImmunoTherapy of Cancer 2016 4:81 (15 November 2016)

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Validation of biomarkers to predict response to immunotherapy in cancer: Volume I — pre-analytical and analytical validation

Giuseppe V. Masucci, Alessandra Cesano, Rachael Hawtin, Sylvia Janetzki, Jenny Zhang, Ilan Kirsch, Kevin K. Dobbin, John Alvarez, Paul B. Robbins, Senthamil R. Selvan, Howard Z. Streicher, Lisa H. Butterfield and Magdalena Thurin
Journal for ImmunoTherapy of Cancer 2016 4:76 (15 November 2016)