Value Propositions - October 2016

October 2016, Vol 7, No 9

In This Article

Melanoma Tumors Use Genetic Mutations to Resist Ipilimumab

New findings show that melanoma tumors use genetic mutations of interferon-gamma (IFN-γ) to resist immunotherapy with ipilimumab (Yervoy), according to a new study in Cell.

"Loss of interferon-gamma (IFN-γ) signaling caused by these mutations is the first clearly defined resistance pathway to ipilimumab found in tumor cells," said study leader Padmanee Sharma, MD, PhD, Director of Immunotherapy Platform, MD Anderson Cancer Center, Houston, TX.

"Research has shown that ipilimumab treatment provides a significant survival benefit in about 20 percent of patients with melanoma," Dr Sharma said. "The mechanisms responsible for the lack of clinical response in the majority of patients have remained unknown."

The researchers evaluated whole-exome genetic-sequencing data for IFN-γ pathway genes in the tumors of patients with melanoma who were receiving ipilimumab. Of the 16 patients evaluated, 4 patients responded to treatment and 12 did not. In the 12 nonresponding tumors, 184 mutations were detected (142 with copy alterations and 42 with single nucleotide variants). By contrast, in the 4 patients who responded, only 4 mutations were found. The nonresponders had an average of 15.33 mutations in IFN-γ pathway genes, with copy number variations providing the significant difference.

Copy number alterations were found in 9 of the 12 nonresponding tumors. Genomic loss of the 2 receptors for IFN-γ—IFNGR1 and IFNGR2—was most significant, along with the downstream genes IRF-1 and JAK2. In addition, SOCS1 and PIAS4, which are known inhibitors of the IFN-γ pathway, were amplified.

"We might be able to stimulate the immune system to produce other cytokines that can overcome tumors with IFN-γ pathway genes turned off," Dr Sharma said.

According to Dr Sharma, the results of this study may lead to the testing of various IFN-γ genes prospectively as a predictor for response to ipilimumab, which, if confirmed, would guide treatment that includes ipilimumab.

Source: Science Daily; September 22, 2016

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NCCN Imaging Appropriate Use Criteria Incorporated into New Century Health's Clinical Support Platform

The National Comprehensive Cancer Network (NCCN) announced that it will integrate the NCCN Imaging Appropriate Use Criteria (AUC) into the New Century Health's value-based clinical decision support platform. This will expand the access to imaging recommendations from the NCCN to practicing oncologists within New Century Health.

"Since 2011, New Century Health has been a licensee of the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for use in Health Information Technology. We appreciate that they will now deliver NCCN Guidelines®-based, qualified imaging AUC to provider groups, health plans, and accountable care organizations throughout the country," said Robert W. Carlson, MD, Chief Executive Officer, NCCN. "Providing NCCN Imaging AUC electronically at point-of-care helps assure quality cancer care for patients with cancer while minimizing unneeded imaging."

There are currently 20 NCCN guidelines available with NCCN Imaging AUC; the entire catalog will be available in 2017.

NCCN Imaging AUC was adapted from NCCN guidelines and is used to support clinical decision-making regarding the use of imaging in patients with cancer. NCCN Imaging AUC outlines the imaging procedures recommended in the guidelines, including radiographs, computed tomography scans, magnetic resonance imaging, functional nuclear medicine imaging, and ultrasound.

"We strongly believe that expanding our strategic collaboration with NCCN strengthens our ability to bring enhanced clinical value to oncologists. Through the use of NCCN Imaging AUC, our participating physicians will be able to ensure that their patients receive the most appropriate imaging at the most appropriate time during the course of treatment," said Atul Dhir, MD, DPhil, Chief Executive Officer, New Century Health, Wellesley, MA.

The Centers for Medicare & Medicaid Services has approved NCCN as a provider-led group for developing Imaging AUC.

Source: National Comprehensive Cancer Network press release; September 15, 2016

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MD Anderson Cancer Center Awarded $19 Million for Funding, Recruitment

The University of Texas MD Anderson Cancer Center received $19 million from the Cancer Prevention & Research Institute of Texas (CPRIT) for recruiting scientists and for research facility funding.

Of the funding awarded, $6 million will be allocated to recruit a senior researcher; $4 million to recruit a Rising STAR (Science and Technology Acquisition and Retention) investigator; and $4 million to recruit 2 first-time, tenure-track faculty members.

The Virginia Harris Cockrell Cancer Research Center at MD Anderson Cancer Center (Science Park) in Smithville, TX, will also receive a $5-million grant for a next-generation sequencing facility.

"CPRIT is a key source of support for MD Anderson's quest to attract top cancer scientists. This important funding, along with the award to augment our Smithville campus, will greatly help further our efforts to end cancer. I am thankful to the State of Texas and CPRIT for their continued recognition of important gains being made in the investigation and treatment of cancer," said Ronald DePinho, MD, President, MD Anderson Cancer Center.

CPRIT was established in 2007 and has provided $1.67 billion to accelerate cancer research in the fight against cancer.

"With these new awards CPRIT continues to build Texas' cancer research capabilities through the recruitment of some of the top minds in cancer research, as well as continuing core research facilities that are shared by researchers to advance science to benefit Texans," said Wayne Roberts, Chief Executive Officer, CPRIT.

Source: The University of Texas MD Anderson Cancer Center press release; September 14, 2016

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Using CAR T-Cells as Targeted Delivery Vehicles for Treating B-Cell Lymphomas

Memorial Sloan Kettering Cancer Center researchers have uncovered new evidence indicating that chimeric antigen receptor (CAR) T-cells, typically used to boost the immune system by helping it to recognize cancer cells as foreign substances, can now be used as "micropharmacies" for targeted delivery of therapy in B-cell lymphomas. The new study was led by Hans Guido Wendel, MD, Memorial Sloan Kettering Cancer Center, New York, NY, and Katrin Tarte, University of Rennes, France.

The research team discovered that mutations in the tumor suppressor HVEM receptor gene––prevalent in approximately 50% of B-cell lymphoma cases-interrupt the interaction with the inhibitory receptor BTLA, which promotes the growth of lymphoma cells. Looking for ways to restore the normal function of the HVEM receptor gene, the researchers found that key molecules in this pathway can be easily targeted with immunotherapy, leading them to engineer a CAR T-cell that could deliver the HVEM protein directly to CD19-expressiong B-cells in animal models. The therapeutic response with these micropharmacies proved more effective than with control CAR T-cells and CD19 CAR T-cells.

This study has important implications for the treatment of B-cell lymphomas and other cancer types, according to the researchers. This new understanding of the potential use of CAR T-cells represents a novel therapeutic approach to repair the HVEM–BTLA interaction and slow the development of lymphoma cells. Furthermore, the findings show that, in addition to attacking cancer cells, CAR T-cells can be used to deliver targeted therapy, which reduces the exposure of toxic therapy to normal cells, thereby reducing the associated side effects of cancer therapy.

Source: Memorial Sloan Kettering Cancer Center press release; September 29, 2016

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