JITC Digest November 2018

Recent Articles

Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis

Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Junsheng Ma, Roland L BassettJr, Noha Abdel-Wahab, Jaime Anderson, Jennifer E Davis, Jocelyn Joseph, Marc Uemura, Ali Noman, Hamzah Abu-Sbeih, Cassian Yee, Rodabe Amaria, Sapna Patel, Hussein Tawbi, Isabella C Glitza, Michael A Davies, Michael K Wong, Scott Woodman, Wen-Jen Hwu, Patrick Hwu, Yinghong Wang and Adi Diab
Journal for ImmunoTherapy of Cancer, 6:103 (11 October 2018)
Research Article

Excerpt:

"Our study provides much-needed data supporting the early use of IFX [infliximab] to hasten irEC [immune-related enterocolitis] symptom resolution, particularly in patients with high-grade colitis."

Fluorine-19 MRI for detection and quantification of immune cell therapy for cancer

Fanny Chapelin, Christian M Capitini and Eric T Ahrens
Journal for ImmunoTherapy of Cancer, 6:105 (11 October 2018)
Review

Excerpt:

"Here, we highlight recent preclinical and clinical uses of perfluorocarbon probes and 19F MRI for adoptive cell transfer (ACT) studies employing experimental T lymphocytes, NK, PBMC, and dendritic cell therapies. We assess the forward looking potential of this emerging imaging technology [Fluorine-19 MRI] to aid discovery and preclinical phases, as well as clinical trials."

Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series

Kendall F. Moseley, Jarushka Naidoo, Clifton O. Bingham, Michael A. Carducci, Patrick M. Forde, Geoffrey T. Gibney, Evan J. Lipson, Ami A. Shah, William H. Sharfman and Laura C. Cappelli 
Journal for ImmunoTherapy of Cancer, 6:104 (11 October 2018)
Case Report

From the Authors

"This case series is the first to describe both diffuse and focal skeletal changes occurring in cancer patients being treated with immune checkpoint inhibitors. With the increasing use of immunotherapy to combat multiple different malignancies, it is important to recognize that immune-related adverse events may also be occurring in bone. With additional research, screening and treatment algorithms are expected to follow."

Kendall F. Moseley, MD — Johns Hopkins University School of Medicine

Targeting VEGFR2 with Ramucirumab strongly impacts effector/ activated regulatory T cells and CD8+ T cells in the tumor microenvironment

Yasuko Tada, Yosuke Togashi, Daisuke Kotani, Takeshi Kuwata, Eichi Sato, Akihito Kawazoe, Toshihiko Doi, Hisashi Wada, Hiroyoshi Nishikawa and Kohei Shitara
Journal for ImmunoTherapy of Cancer, 6:106 (11 October 2018)
Research Article

Excerpt:

"Our study is the first to utilize human clinical samples to highlight the significance of TIL [tumor-infiltrating lymphocytes] analyses and to propose RAM [ramucirumab] as an immuno-modulator in combination with ICB [immune checkpoint blockade]."

Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab

Haris Zahoor, Pedro C. Barata, Xuefei Jia, Allison Martin, Kimberly D. Allman, Laura S. Wood, Timothy D. Gilligan, Petros Grivas, Moshe C. Ornstein, Jorge A. Garcia and Brian I. Rini
Journal for ImmunoTherapy of Cancer, 6:107 (17 October 2018)
Research Article

From the Authors

"Our series on nivolumab-treated RCC patients provides some valuable real world data on the performance of this drug in the clinic. We discovered patters of progression in patients (more often brain) as well as factors associated with improved outcome. We hope these data assist caregivers in using nivolumab in RCC."

Brian I. Rini, MD — Cleveland Clinic Taussig Cancer Center

Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement

Apostolia M. Tsimberidou, Laura A. Levit, Richard L. Schilsky, Steven D. Averbuch, Daniel Chen, John M. Kirkwood, Lisa M. McShane, Elad Sharon, Kathryn F. Mileham and Michael A. Postow
Journal for ImmunoTherapy of Cancer, 6:108 (19 October 2018)
Position Article and Guidelines

From the Authors

"The TRIO recommendations are designed to standardize the reporting, as a result of the conduct of clinical trials in Immuno-Oncology (IO). These trials are essential in developing and optimizing the use of immunotherapeutic strategies. As the number of clinical trials with these treatments continues to substantially increase, ASCO formed a working group in collaboration with SITC to develop the TRIO recommendations. The goal is to fill a current void in how we uniformly account for the reporting of the design, conduct, analysis, and results of IO clinical trials. The 12 specific reporting recommendations provide useful and practical guidance to the immuno-oncology community to improve the interpretation and comparison of efficacy and toxicity endpoints and the combination and sequencing of treatments in IO clinical trials. It is our hope that the research community, and biomedical journals specifically, will adopt these recommendations to promote understanding and comparison across IO trials and improve the quality of IO trial reporting and assessment."

Apostolia M. Tsimberidou, MD, PhD — MD Anderson Cancer Center

A severe case of neuro-Sjögren’s syndrome induced by pembrolizumab

Jaqueline Ghosn, Alex Vicino, Olivier Michielin, George Coukos, Thierry Kuntzer and Michel Obeid
Journal for ImmunoTherapy of Cancer, 6:110 (22 October 2018)
Case Report

From the Authors

"This case demonstrates that in some patients, a particular type of connective tissue disease (CTD) can be “de novo” induced by immune checkpoint inhibitors (CPIs) with no prior clinical or laboratory evidence of autoimmune disorders. The important B/plasma cell CD20+ infiltrate component on the accessory salivary glands biopsy ASGB (around 25%) and the presence of autoantibodies, were used as a rational target for an anti-B-cell strategy (by rituximab mAbs). Not only has this targeted strategy been clinically effective but also in the minimizing the risk of melanoma recurrence and T cell suppression."

Michel Obeid, MD, PhD — Lausanne University Hospital CHUV

Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study

Asim Amin, Elizabeth R Plimack, Marc S Ernstoff, Lionel D Lewis, Todd M Bauer, David F McDermott, Michael Carducci, Christian Kollmannsberger, Brian I Rini, Daniel Y C Heng, Jennifer Knox, Martin H Voss, Jennifer Spratlin, Elmer Berghorn, Lingfeng Yang and Hans J Hammers
Journal for ImmunoTherapy of Cancer, 6:109 (22 October 2018)
Research Report

From the Authors

"The phase I CheckMate 016 study assessed the safety and efficacy of nivolumab in combination with ipilimumab, or the VEGF tyrosine kinase inhibitors (TKIs) sunitinib or pazopanib. Here we present outcomes for the nivolumab plus sunitinib or pazopanib arms with long-term follow-up. Efficacy outcomes with both of the nivolumab plus TKI combinations were notable, including ORR of 55% with nivolumab plus sunitinib and 45% with nivolumab plus pazopanib, as assessed by investigators. The duration and depth of response observed in the nivolumab plus sunitinib arm after 50.0 months median follow-up are impressive (longest median follow-up available for any immune checkpoint inhibitor [ICI] and TKI combination to date). However, both of the nivolumab plus TKI regimens were associated with a high incidence of high-grade toxicities in combination with the standard dose and schedule of sunitinib or pazopanib. These results serve as proof-of-concept for other trials of different ICI plus TKI combinations in patients with aRCC that are currently ongoing."

Asim Amin, MD, PhD — Levine Cancer Institute - Carolinas Medical Center

Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial

Christophe Le Tourneau, Christopher Hoimes, Corrine Zarwan, Deborah J. Wong, Sebastian Bauer, Rainer Claus, Martin Wermke, Subramanian Hariharan, Anja von Heydebreck, Vijay Kasturi, Vikram Chand and James L. Gulley
Journal for ImmunoTherapy of Cancer, 6:111 (22 October 2018)
Research Report

From the Authors

"Our study shows that targeting PD-L1 with avelumab provides antitumor activity in patients with adrenocortical carcinoma, especially in patients whose tumor expresses PD-L1. This is an important finding in a disease in which treatment options are limited."

Christophe Le Tourneau, MD, PhD — Institut Curie

Neoadjuvant ipilimumab (3 mg/kg or 10 mg/kg) and high dose IFN-α2b in locally/regionally advanced melanoma: safety, efficacy and impact on T-cell repertoire

Ahmad Tarhini, Yan Lin, Huang Lin, Zahra Rahman, Priyanka Vallabhaneni, Prateek Mendiratta, James F. Pingpank, Matthew P. Holtzman, Erik C. Yusko, Julie A. Rytlewski, Uma N. M. Rao, Robert L. Ferris and John M. Kirkwood
Journal for ImmunoTherapy of Cancer, 6:112 (23 October 2018)
Research Report

From the Authors

"Neoadjuvant immunotherapy with interferon-α combined with CTLA4 blockade exhibited promising radiologic as well as pathologic tumor response rates. There was an associated significant impact on T-cell fraction and clonality within the tumor microenvironment and the circulation. Pathologic complete responses (pCR) were durable supporting the value of pCR as a primary endpoint in neoadjuvant immunotherapy trials in melanoma."

Ahmad A. Tarhini, MD, PhD — Cleveland Clinic Taussig Cancer Institute

Paraneoplastic hyperleucocytosis in a melanoma patient after initiation of ipilimumab and nivolumab combination therapy

Thilo Gambichler, E. Stockfleth and L. Susok
Journal for ImmunoTherapy of Cancer, 6:113 (30 October 2018)
Case Report

Excerpt:

"Although PH may be a rare complication of combined anti-CTLA-4 and anti-PD1 immunotherapy, it is nevertheless of importance given the fact that this treatment modality is increasingly used also in adjuvant settings and other malignancies such as colorectal cancer and renal cell carcinoma."

CD33/CD3-bispecific T-cell engaging (BiTE®) antibody construct targets monocytic AML myeloid-derived suppressor cells

Regina Jitschin, Domenica Saul, Martina Braun, Sehmus Tohumeken, Simon Völkl, Roman Kischel, Michael Lutteropp, Cedric Dos Santos, Andreas Mackensen and Dimitrios Mougiakakos
Journal for ImmunoTherapy of Cancer, 6:116 (5 November 2018)
Short Report

Excerpt:

"In this study we sought out to investigate whether AMG 330 could simultaneously confer two hits by redirecting T-cells against both CD33+ AML-blasts and CD33+ MDSCs thereby further enhancing anti-leukemic immune activity."

Highly Accessed Articles

Ibuprofen supports macrophage differentiation, T cell recruitment, and tumor suppression in a model of postpartum breast cancer

Nathan D. Pennock, Holly A. Martinson, Qiuchen Guo, Courtney B. Betts, Sonali Jindal, Takahiro Tsujikawa, Lisa M. Coussens, Virginia F. Borges and Pepper Schedin
Journal for ImmunoTherapy of Cancer 2018, 6:98 (1 October 2018)

Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study designed for rapid clinical signal assessment metastatic castration-resistant prostate cancer

Jason M. Redman, Seth M. Steinberg and James L. Gulley
Journal for ImmunoTherapy of Cancer 2018, 6:91 (18 September 2018)

Local angiotensin II contributes to tumor resistance to checkpoint immunotherapy

Guozhu Xie, Tan Cheng, Jie Lin, Lanfang Zhang, Jieling Zheng, Ying Liu, Guobo Xie, Baiyao Wang and Yawei Yuan
Journal for ImmunoTherapy of Cancer 2018, 6:88 (12 September 2018)

Letter from the Editor

Dear JITC Readers,

In the November edition of the JITC Digest, there are three noteworthy articles of which I wish to draw special attention. First, the joint SITC-ASCO clinical trial reporting guideline, “Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement,” by Apostolia M. Tsimberidou et al. presents 12 specific recommendations which address the many unique aspects of immuno-oncology therapies. Based on expert consensus, this statement provides practical recommendations to improve IO clinical trial design, conduct, analysis, and results reporting. Given the rapid expansion of IO clinical trials and the limited data in support of evidence-based recommendations, TRIO is intended to help clinical trials provide more complete evidence regarding the relative benefits and risks of immunotherapy approaches.

Next, the article, “Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab,” by Haris Zahoor et al. details a retrospective analysis of patients with metastatic clear cell renal cell carcinoma (ccRCC) treated with nivolumab at Cleveland Clinic over a two year period. This study highlights the fact that although approval of nivolumab has been practice changing in the treatment of metastatic RCC, only a subset of patients benefit from this therapy. Here, Dr. Zahoor’s group examines patterns of progressive disease and patient outcomes in order to identify predictive biomarkers to improve patient response and better understand disease progression for ccRCC patients outside of a clinical trial.

Finally, Fanny Chapelin et al.’s review, “Fluorine-19 MRI for detection and quantification of immune cell therapy for cancer,” provides an overview of current and emerging strategies to detect adoptive cell therapy (ACT) activity using fluorine-19 magnetic resonance imaging (19F MRI). This review highlights recent preclinical and clinical uses of 19F MRI - such as monitoring of therapeutic cell survival and trafficking to tumor sites - and suggests an important role for noninvasive imaging of immune cell therapy in vivo for development of real-time, quantitative biomarkers for ACT. Potential benefits in regards to advancing cell therapy trials as well as logistical limitations towards development and adoption of this technology are discussed.

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