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Saturday, June 2, 2018

NantHealth presents sequencing study at #ASCO18


Results to be presented during the tumor biology session at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting
NantWorks, LLC today announced that its affiliate companies, NantHealth, Inc., (NASDAQ: NH), a leading next-generation, evidence-based, personalized healthcare company and NantOmics, LLC, the leader in molecular analysis and a member of the NantWorks ecosystem of companies, will present findings on how 17 percent of next generation sequencing (NGS) 50 gene panel variants are not expressed in RNA sequencing during the tumor biology session at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting, an event bringing together 30,000 oncology professionals from June 1-5, 2018 at McCormick Place in Chicago, Illinois. NantWorks will be exhibiting at booth #7147 during the event.
“By determining the frequency of non-expressed variants that would be tested by a standard NGS panel, our data shows that the identification of these genes can yield improved testing algorithms and treatment strategies,” said Patrick Soon-Shiong, MD, founder of NantWorks. “We’re excited to share this data and look forward to further exploring how NGS can be used for target therapy in oncology.”
Presentation Details
Seventeen percent of NGS 50 gene panel variants are not expressed in RNAseq, Abstract #12118
WHO: NantHealth, LLC and NantOmics, LLC
WHAT: Tumor Biology Session
WHEN: June 4, 1:15-4:45 PM CST
WHERE: Hall A, McCormick Place
Presentation Summary
This study analyzed the frequency of non-expressed variants that would be tested by a standard NGS panel through retrospective analysis of a database from a commercial DNA tumor: normal and RNAseq platform. In the 992 samples that were identified with paired DNA (WGS or WES) / RNAseq NGS, a total of 225,727 SNVs were detected. Across 37 tumor types the range of expression was 57% (melanoma) – 100% (uterine). In this analysis, 17 percent of detected variants were not expressed in the RNA sequence. As a result, the lack of RNA expression may contribute to less than expected clinical benefit with molecularly targeted therapies. Since the distribution is non-uniform, identification of these genes can yield improved testing algorithms and treatment strategies.

New heart attack category more common in women than previously thought


A whole new category of heart attack, not caused by obstructed arteries, is more common and higher risk–especially in women–than previously thought, according to a University of Alberta study.
“We followed roughly 36,000 patients within a 12-year interval and found that close to a surprising six per cent have a heart attack without any blockage in the arteries,” said Kevin Bainey, a U of A interventional cardiologist who launched the study after seeing an increase in these mystery patients in his practice.
The umbrella term used to describe these heart attacks is “myocardial infarction with non-obstructive coronary arteries,” or MINOCA.
“Historically, MINOCA has been seen as a benign condition, and patients are commonly sent home without any treatment or lifestyle advice,” he explained. “Yet we found that after one year’s time, five per cent of patients either had another heart attack or died of a heart attack. This is striking, since patients with a plugged coronary artery have a nine per cent chance of a repeat attack or death within one year.”
The study is the first in the world to look at MINOCA over a long term. Bainey said the condition includes a range of less-understood heart attack causes that have been largely treated as benign.
“Not only did we find that prognosis only worsens over time, after five years, 11 per cent of MINOCA patients were likely to die or have a second heart attack compared with 16 per cent of heart patients with blocked arteries,” noted Bainey.
MINOCA patients were twice as likely to be female, according to the study.
“We found roughly 25 per cent of common heart attack patients are female, whereas 50 per cent of MINOCA patients are female,” said Bainey, adding that it is not clear why this is the case.
“Traditionally, because we haven’t seen plaque ruptures or blockages are not seen, physicians have tended to downplay the heart attack and provide limited information, and have sent patients home and told them not to worry,” said Bainey. “However, many of the MINOCA causes that are known do respond to targeted therapies.”
Yet the study showed that only 40 per cent of MINOCA patients are provided with suitable medications–for example, cholesterol-lowering drugs–that could potentially reduce the risk of a second heart attack or death.
“Patients need to know that this condition is real, it is associated with adverse outcomes and they need to probe their physicians for more information about the condition and ways to prevent a second heart attack, including making important lifestyle changes like eating healthier and exercising,” said Bainey.
“From a physician standpoint, there is no question that when we identify this condition, we need to be more vigilant about trying to investigate and pin down the cause.”
Last year, the condition was recognized in guidelines by the European Society of Cardiology for major heart attacks.
The study was published in the International Journal of Cardiology and funded through the Canadian VIGOUR Centre.
What is MINOCA?
Women are more susceptible to a group of heart attack causes not related to blocked arteries, although it’s not clear why, according to U of A interventional cardiologist Kevin Bainey.
Though researchers are still investigating potential causes, they have identified the following:
  • a tiny rupture or tear in the artery, known as SCAD (spontaneous coronary artery disruption), that isn’t visible without specialized equipment
  • small amounts of plaque buildup and clot not visible during a coronary angiogram
  • inflammation of the heart muscle
  • stress-induced heart muscle dysfunction

The Unappreciated Key to Success


The most unappreciated element in success in any area of life–trading or otherwise–is the capacity to sustain effort.  We can think of this capacity as intentionality:  the ability, over time, to exercise free will.
For much of daily life, we follow routines.  This is efficient, allowing us to get the most done with the least effort.  A great example is driving a car.  Being able to do that automatically enables us to carry on conversations, listen to music or podcasts, etc. The problem occurs when we become so immersed in routine–so wedded to getting the most done with the least effort–that we are unable to sustain the efforts that generate distinctive performance.
Important research from the psychologist Mihalyi Csikszentmihalyi identified a “flow state” in which people become capable of high levels of creativity.  The flow state results from being immersed in efforts over time–a kind of hyperfocus.  In that state of superfocus, we become capable of processing information in new ways, seeing patterns and solutions that escape us in our normal state of awareness.
In our ordinary state of mind, we can only achieve ordinary things.  All success comes from the ability to transcend routine.  But that requires effort and the capacity to sustain effort.  Successful people have developed routines that exercise intentionality:  that build the capacity to sustain flow states.  They sustain those efforts by pursuing their strengths: what they are good at and what speaks to them.  We achieve hyperfocus when we are hyper-interested in what we are doing.  If you need discipline to get things done, you know you are not operating in the sphere of your strengths and passions.

Dimon: Health insurers griped to him on Amazon-Berkshire deal


  • Dimon says that irate healthcare companies called him to complain about joint venture
  • Healthcare effort has a 20-year horizon and seeks to lower costs, improve service, he says
  • Dimon: “They’re going to tell me I can’t do a better job for my employees? Isn’t that what they’re supposed to help me do anyway?”
J.P. Morgan Chase CEO Jamie Dimon has been on the receiving end of some testy phone calls recently.
After he and fellow billionaires Amazon‘s Jeff Bezos and Berkshire Hathway’s Warren Buffett announced the formation of a joint venture in January to reduce medical costs for their three companies’ 1.5 million insured employees, several healthcare-related providers reached out to Dimon personally, he said Friday during a New York conference.
“Quite a bit of them were pissed off, which kind of pissed me off,” Dimon, 62, said. “They’re going to tell me I can’t do a better job for my employees? Isn’t that what they’re supposed to help me do anyway? That’s all we’re trying to do, is do a better job for the health of our employees.”
The effort, spearheaded by Berkshire Hathaway executive and J.P. Morgan board member Todd Combs, has yet to settle on a CEO. After that happens, the venture will begin testing ideas to attack the myriad problems related to the rising costs of American healthcare, Dimon said. When the effort was announced January 30, the shares of pharmacy benefit managers, heath insurers and biotechnology companies all slumped.
The effort has a 20-year horizon and seeks to partner with companies within the healthcare ecosystem, Dimon said. Among issues to tackle are related to use of data, lack of consumer choice, high costs related to fraud and administrative costs, end of life care, and lifestyle-related diseases, he said.
“They could attack it one drug at a time, they could attack chronic care, they could attack emergency rooms,” Dimon said. “There will be things we will come up with that we couldn’t possibly think of today that will hopefully make it much better.”

Foundation Med, Partners at #ASCO18 on Comprehensive Genome Profiling, Cancer


 Foundation Medicine, Inc. (NASDAQ:FMI) announced that new data generated from its comprehensive genomic profiling (CGP) assays will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting from June 1-5, 2018 in Chicago. The company and its collaborators will present a total of 28 studies, including two oral presentations. Highlights of these presentations include:
  • studies demonstrating the importance of known and novel genomic biomarkers of immunotherapy response, including tumor mutational burden (TMB), microsatellite instability (MSI) and PBRM1 alterations across a diverse range of cancer types that could inform more precise use of these treatments;
  • new data from PURE-01, a phase II study evaluating neo-adjuvant pembrolizumab in urothelial bladder cancer demonstrates the ability of CGP to detect genomic biomarkers (RB1PBRM1 and TMB) when combined with T-cell inflammation signatures to potentially predict response to immunotherapy;
  • new data showing that high tissue TMB is associated with higher likelihood of response and longer duration of response to atezolizumab in non-small cell lung cancer, metastatic urothelial carcinoma and melanoma;
  • data from FoundationACT® liquid biopsy assay, describing the landscape of kinase fusions and rearrangements from ctDNA in more than 9,000 clinical cases across multiple cancer types; and
  • updated data from the precision oncology I-PREDICT clinical trial showing improvements in patient outcomes with integration of molecular tumor boards informed by CGP into treatment planning.

New Wave in Neurology/Stroke Care


Andrew N. Wilner, MD: Welcome to Medscape. I am Dr Andrew Wilner, and I am at the 2018 American Academy of Neurology (AAN) meeting in Los Angeles. I have the pleasure to be joined by Dr Terry Detrich. Dr Detrich has been a frequent attendee at the AAN meetings and is still in practice.
Thanks for joining me, Terry. I would like to talk with you about the AAN meetings and have you share your insights on how the meeting has changed over the years, in particular with respect to its value to neurologists.
Terry P. Detrich, MD: Thank you for having me.
Wilner: When we spoke last night, I could see how very excited you are about the meeting.
Detrich: Every time I attend an AAN meeting, there is new information that changes my practice. I am very patient-oriented, and when I attend these meetings, I look for information that will enhance the care of my patients.
I see myself as a buffer between unrealistic and realistic [patient] expectations and reality. When things change—and they are changing rapidly—I want to be part of these changes, incorporate them into my practice, and deliver the latest care recommendations to my patients as soon as possible.
I have been very active in the management and treatment of stroke, and I just recently retired as medical director of a stroke center at a small rural hospital. Following the approval of tissue plasminogen activator (tPA), my colleagues and I have been very successful in treating stroke patients. I was actually with Michael Walker, MD, at the 1995 AAN meeting in San Francisco when he and his colleagues presented the tPA data. This [treatment] changed my life and the lives of my patients; it also changed our hospital’s healthcare delivery system.
For a primary hospital, my institution has been incredibly successful in its care of stroke patients. Our hospital system sees approximately 225 stroke patients a year. This past year, we won the American Heart Association/American Stroke Association Get With The Guidelines-Stroke Gold-Plus Quality Achievement Award for stroke care, and our use of tPA has gone up substantially owing to the support of our emergency physicians. My institution is affiliated with the University of Maryland, which helped us with [stroke care] coverage.
The MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands)[1] was the beginning of the changes in stroke care. Yesterday, the data that were presented fromthe DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention)[2] and the DEFUSE 3 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 3)[3] trials provided a new perspective on stroke care delivery.
Wilner: These trials suggest that thrombectomy now can be performed up to 24 hours after an ischemic stroke—a new wave of ways to help patients.
Detrich: It is an incredible new wave of care. There will be a lot of growing pains in implementing these new changes to stroke care, and we have already begun to address some potential problems in this regard at my institution.
For example, we cannot send all stroke patients to a tertiary facility—there are not enough beds to do so. At our institution, located in a small town in Maryland, we are going to select our patients, prestudy them, and move the transfer through the use of telemedicine. We have a great transport system, in part based on our shock-trauma unit, which I believe was the first in the country. We have an extensive medical evacuation system already in place, and are ultimately looking at a telemedicine program. We have not been able to expand in the way that I would like in regard to telemedicine, but I have the whole medical team on board, thanks in part to the great coordinators with whom I work.
We also will need advanced imaging modalities to assess perfusion or perfusion/diffusion mismatches to determine which patients require transport to a tertiary center.
As I mentioned, we are very big on administering tPA to stroke patients and have had outstanding treatment successes. This past year, I believe all of our stroke patients received tPA within 60 minutes We are thrilled with and proud of our achievements.
For 20 years, there were no changes in stroke care. I did not even bother to go to any of the stroke sessions at the AAN meeting. My perspective changed when the tPA data were presented. Now I always attend the stroke sessions to keep up with the latest trial data, the direction care is heading, and the latest standard of care.
I am overwhelmed by the data [from DAWN and DEFUSE 3] and the impact these will have on our patients over the next few years. I do have concerns about the increasing cost, an issue that also was raised by others yesterday. Providing 24/7 care for patients is a big deal. We do not have enough stroke doctors or stroke trainees to offer this type of coverage. Another concern related to cost is specifically who is going to pay for this care.
Although the selected group of patients in each of the two trials was small, the outcomes were spectacular.[2,3] These outcomes may be compared with studies showing the effectiveness of catheterization in preventing myocardial infarction (MI). It took 22 patients to get a catheter study to prevent an MI to have dramatic improvement in stroke in this selected group.
With respect to the DAWN and DEFUSE 3 trials, we have to keep in mind that the results were seen in a selected group of patients. It was between two and three patients to get outstanding results. These outstanding results were that the patients were alive and had a modified Rankin scale score of 2 or less, indicating at least self-care or even the ability to return to work and function normally. That is pretty outstanding.
Wilner: What other information from the AAN meeting are you going to share with your patients?
Detrich: I was blown away by the results of some of the gene-modifying trials that were reported. I had an off-label, anecdotal conversation with some of my colleagues in the genetics field about their experiences with gene modification for Huntington disease and amyloid beta modification. I have patients with amyloid disease and patients with Huntington disease, so [I was excited] to hear these anecdotal reports on the possibility of genetic modification in Friedreich ataxia.
I thought these research findings would take 20 years, which was a realistic expectation when I started in practice. Now things are happening so quickly. With all the basic science, with all the technical advances, with all the experience, this has come about in a matter of 2-3 years from what was postulated.
It is great to have this type of data to share with patients. In fact, I have an informal discussion scheduled in May to talk with staff, patients, and caregivers about what is new in neurology. I am thrilled to talk about this with them.
Wilner: With your level of interest and enthusiasm, I do not see retirement in your near future.
Detrich: Well, I retired from private practice, but am working full-time. In my practice, I focused more on what I will call “geriatric neurology,” though more on movement disorders and dementias.
In addition to the changes that are taking place in diagnoses [of neurologic diseases], new therapies are not that far away. We are finally at a point where we are sorting through all these conditions.
I am an old man who has been in practice for a long time. Now, after all of the information presented at the AAN meeting, I am rethinking Parkinson disease. For example, I no longer view Parkinson disease as a dopamine deficiency disease, but rather as an alpha-synucleinopathy. This perspective explains a lot of my clinical observations. I am both thrilled and excited to share some of this new information with my staff and my patients and their caregivers.
Wilner: Dr Detrich, I share your enthusiasm, and that is also why I attend the AAN meetings. Now that we have tools to help our patients, I think more and more physicians are going to stay in practice longer. We finally have the ability to help patients and change the ill-deserved reputation that neurologists had a long time ago.
Detrich: I can talk about that too, because I was there a long time ago and remember the “diagnose and adios” reputation we had. As you know, the decade of the brain in the 1990s changed neurology from being a diagnostic specialty to a therapeutic specialty. I was very enthusiastic and excited about this. The big thing then, when we look at the long term, was disease-modifying therapies in multiple sclerosis.
I was very hopeful in the 2000s, but became a little frustrated in early years of the 2010s. Now, with all this new information, technology, and potential new treatments over the past couple of years, I am rejuvenated, anticipating that next step at the bedside. There are actually ongoing clinical trials for tau and for alpha-synuclein. I want to be part of that, which is why I want to continue to practice.
Wilner: I want to thank Dr Detrich for joining me here at the annual AAN meeting in Los Angeles. I am Dr Andrew Wilner, reporting for Medscape.

Adaptimmune: #ASCO18 presentation data further supports med benefit


Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, presented initial data from the ongoing pilot study of NY-ESO SPEAR T-cells in myxoid/round cell liposarcoma (MRCLS). With eight patients treated, the best overall responses include three confirmed partial responses, one unconfirmed partial response, three stable disease, and one recently treated patient awaiting assessment. These data were presented during an oral presentation by Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center at the American Society of Clinical Oncology (ASCO) annual meeting.
GlaxoSmithKline plc (LSE:GSK) (NYSE:GSK) exercised its option to exclusively license the right to research, develop, and commercialize the NY‑ESO SPEAR T-cell therapy program in September 2017. Transition of this program to GSK is ongoing.
“We continue to see responses in patients with advanced MRCLS who have failed previous standard chemotherapy,” said Rafael Amado, Adaptimmune’s Chief Medical Officer. “We observe significant proliferation of our SPEAR T‑cells in peripheral blood, and infiltration into metastases that were previously devoid of inflammatory cells. These findings bode well for a broad therapeutic potential of SPEAR T‑cells across multiple solid tumors.”
Data Update from the Ongoing NY-ESO MRCLS Study
During an oral presentation on June 2nd entitled, “Pilot Study of NY-ESO-1c259T Cells in Advanced Myxoid/Round Cell Liposarcoma,” Dr. D’Angelo presented an update from this ongoing study (data cut-off May 23 2018).
  • Responses:
    • Best overall responses include 3 confirmed partial responses, 1 unconfirmed partial response, 3 patients with stable disease, and 1 recently treated patient awaiting assessment
    • There is an overall trend in tumor burden decrease among the majority of patients
    • The tumor burden decrease across target lesions ranged from 16.9% to 50%
    • Three patients have now progressed
  • Safety: Thus far, data indicate that NY-ESO SPEAR T-cells remain generally well tolerated in this patient population:
    • There was one event of cytokine release syndrome (CRS) ≥ Grade 3, which was characterized by fever, hypotension, rash, headache, and supraventricular tachycardia. The patient was treated with tociluzumab. The CRS resolved six days post-infusion.
    • There were four SAEs reported by three patients:
      • Grade 3 CRS (noted above), which resolved
      • Two Grade 2 events of CRS, both of which resolved
      • Grade 2 pleural effusion, which improved with treatment and the patient was subsequently discharged from hospital
    • Most adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or cancer immunotherapies
  • SPEAR T-cell persistence: Although data are preliminary, there appears to be a correlative trend between SPEAR T-cell persistence and response.
The Company will host a live teleconference to answer questions about the updated safety data on June 4, 2018 at 8:00 a.m. EDT (1:00 p.m. BST). The live webcast of the conference call will be available via the events page of Adaptimmune’s corporate website at https://bit.ly/2shwniM. An archive will be available after the call at the same address. To participate in the live conference call, if preferred, please dial please dial +1-(833) 652-5917 (U.S.) or +1-(430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (9199456).