ASH Clinical News ACN_4.8_Final_digital | Page 28

Researchers announced the completion of the PanCancer Atlas , an NIH-funded , detailed genomic analysis of molecular and clinical information collected from more than 10,000 tumors , representing 33 cancers .

“ This project is the culmination of more than a decade of groundbreaking work ,” said NIH Director Francis S . Collins , MD , PhD . “ This analysis provides cancer researchers with unprecedented understanding of how , where , and why tumors arise in humans , enabling better-informed clinical trials and future treatments .”

Results of the PanCancer Atlas were published as a collection of 27 papers in Cell . The PanCancer Atlas is divided into three main categories : cell of origin , oncogenic processes , and oncogenic pathways .

The first summary paper details a set of analyses of molecular clustering , which groups tumors by parameters such as genes being expressed , abnormality of chromosome numbers in tumor cells , and DNA modifications . The findings suggest that tumor types cluster by their possible cells of origin .

— FRANCIS S . COLLINS , MD , PhD

The second summary paper presents a broad view of The Cancer Genome Atlas ( TCGA ) findings on the processes that lead to cancer development and progression . The researchers identified three oncogenic processes : mutations , both germline and somatic ; the influence of the tumor ’ s underlying genome and

epigenome on gene and protein expression ; and the interaction between tumor and immune cells .

The third summary paper details TCGA investigations into the genomic alterations in the signaling pathways that control cell cycle progression , cell death , and cell growth . The findings revealed new patterns in the potential vulnerabilities of malignancies .

The researchers hope that these findings could lead to the development of new and personalized treatment options .

Source : National Cancer Institute press release , April 5 , 2018 .

CVS Health introduced the Rx Savings Finder : A system that can check for lessexpensive medications , higher quantities at lower costs , and drug discounts to potentially decrease costs for patients and encourage treatment adherence .

“ The power of this tool … is we have access to the information that we need to be able to provide options to our customers to save them money ,” said Kevin Hourican , executive vice president of retail pharmacy at CVS .

With this system , pharmacists can compare prices and view less-expensive alternatives , such as generic drugs . During the pilot phase , CVS found that 95 percent of patients and 85 percent of doctors opted into the program .

The pharmacy system will initially be available to patients who use CVS ’ pharmacy benefits manager , Caremark , and the system is expected to become available to other major payers this summer .

Source : CNBC , April 10 , 2018 .

The U . S . Food and Drug Administration ( FDA ) finalized two guidance documents on recommendations for designing , developing , and validating tests that use next-generation sequencing ( NGS ) technology .

“ As disease-detection technologies rapidly evolve , so too must the FDA ’ s approach to reviewing these new innovations ,” said FDA Commissioner Scott Gottlieb , MD . The first guidance , titled “ Use of

Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics ,” provides product developers with FDA-recognized public databases and direction on how to use these data to support the clinical validation of the NGS tests they are developing .

The second guidance , titled “ Considerations for Design , Development , and Analytical Validation of Next Generation Sequencing ( NGS )– Based In Vitro Diagnostics ( IVDs ) Intended to Aid in the Diagnosis of Suspected Germline Diseases ,” describes what the agency expects in design , development , and validation of NGS-based tests in premarket submissions to determine a test ’ s analytical validity . This includes how well the test detects the presence or absence of a particular genomic change .

These guidance documents are based on feedback from the public and stakeholders developing NGS-based technologies . They serve as a framework for the agency ’ s creation of regulatory efficiencies in the development and review of NGS tests .

Source : U . S . Food and Drug Administration press release , April 12 , 2018 .

The FDA has expanded the approval of the chimeric antigen receptor ( CAR ) T-cell therapy tisagenlecleucel to include the treatment of patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy . The indication includes diffuse large B-cell lymphoma ( DLBCL ), high-grade B-cell lymphoma , and DLBCL arising from follicular lymphoma .

In August 2017 , tisagenlecleucel became the first FDA-approved CAR T-cell therapy when it received approval for the treatment of patients aged 25 years or younger with B-cell precursor acute lymphocytic leukemia ( ALL ) that is refractory or in second or later relapse . With the recent expanded approval , it is now the only CAR T-cell therapy approved for two distinct indications .

The decision was based on results from the phase II JULIET trial , which were presented at the 2017 ASH Annual Meeting by Stephen J . Schuster , MD . Among the 68 JULIET participants evaluable for efficacy , half responded to treatment , with 32 percent of patients achieving a complete response and 18

percent achieving a partial response . The median duration of response was not reached .

Cytokine release syndrome , a potentially fatal adverse event ( AE ) associated with CAR T-cell therapy , occurred in 23 percent of 106 patients treated with tisagenlecleucel . Eighteen percent of all infused patients experienced grade 3 / 4 neurologic events , including 11 percent who experienced encephalopathy . Neurotoxic AEs were managed with supportive care and there were no deaths attributed to neurologic events , the investigators reported .

Novartis , the manufacturer of tisagenlecleucel , also announced a new “ indication-based ” pricing model for the therapy : When used to treat lymphoma , tisagenlecleucel costs $ 373,000 , compared with $ 475,000 for the same therapy when used to treat ALL . This controversial type of pricing sets costs based on the relative population frequency of approved indications , rather than distinct development or manufacturing costs or market forces .

Sources : Novartis press release , May 1 , 2018 ; FDA press release , May 1 , 2018 .

The FDA granted approval to andexanet alfa , also known as coagulation factor Xa ( recombinant ), inactivated-zhzo , for the reversal of the anticoagulant effects of rivaroxaban and apixaban . This agent is the first FDA-approved antidote for these newer factor Xa inhibitors , and is indicated for use when patients require rapid reversal of anticoagulation due to life-threatening or uncontrolled bleeding .

The FDA ’ s decision is based on findings from two phase III trials from the ANNEXA program , which evaluated the safety and efficacy of andexanet alfa in healthy volunteers . Rivaroxaban-treated patients experienced a median decrease in anti – factor Xa activity from baseline of 97 percent ; anti – factor Xa decreased a median of 92 percent in apixaban-treated patients .

The most common AEs in patients receiving andexanet alfa included urinarytract infections , pneumonia , and infusionrelated reactions .

Arterial and venous thromboembolic events , ischemic events , sudden deaths , or instances where a thrombotic event could not be ruled out were observed within 30