Wednesday, March 7, 2018

You Say You Want A Revolution? Cancer Patients Gently Wrest Control of Groundbreaking Immunotherapy Conference



A deep-orange sunrise sky ricocheting off San Diego Bay warmly greeted a contingent of some of the world’s brightest cancer scientists, oncologists, pharmaceutical executives and patients as they arrived last month in Coronado, Calif., to attend the two-day ImmunoTX Summit, a global immunotherapy conference.

Immunotherapy, also known as immuno-oncology, immunology, or just IO, is the century-old effort to harness the body’s immune system to fight cancer. This once-disrespected stepchild of the cancer research world has finally gained respectability, and then some.

Proving the array of skeptics wrong, IO is now being hailed even by its many former naysayers as the most significant breakthrough in cancer treatment that modern medicine has ever seen. There’ve been multiple breakthroughs in just the last year, and the summit addressed the very latest advances.

IO doesn’t yet work for every patient, or every cancer, but the percentages of complete remissions among patients in clinical trials and now in the clinic are unprecedented, for several types of cancer.

IO appears primed to become the so-called fifth pillar among the staples of cancer treatment -- chemotherapy, radiotherapy, surgery, and other targeted therapies -- and will before long likely and hopefully be the dominant one of the five.

Currently the brightest star in the IO sky is chimeric antigen receptor T-cell therapy -- better known simply as CAR-T. A technology that was first happened upon some 30 years ago, CAR-T involves the body’s T cells, which essentially are our immune system.

During the CAR-T process, these cells are culled from the patient’s blood, engineered with new proteins that allow them to recognize cancer, and reinfused in the patient in very large numbers.

The jacked-up cells proceed to find and attack your cancer, and, remarkably, they persist in the body, becoming “living drugs.”

In August, Kymriah, a CAR-T from Novartis, was approved for a type of childhood leukemia. In October, Yescarta, a CAR-T from Gilead, was approved for B cell lymphomas. And in late January, Kymriah was given fast-track attention by the FDA for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Many more treatments are moving swiftly through the regulatory process, including JCAR017, Juno and Celgene’s very promising CAR-T for aggressive B-cell non-Hodgkin’s lymphoma which the data show as the best in class, especially in terms of safety.

There are reportedly some 25o clinical trials for various CAR-T technologies, and thousands more for other immunotherapeutic agents and various regimens that combine IO drugs with other treatments.

Scientists and Patients Get the Star Treatment

You couldn’t have spent more than five minutes at the ImmunoTX Summit without concluding that this is a watershed moment in the history of cancer treatment, and a game-changing time for cancer patients. 

The positive buzz at the conference was palpable. And why not?

As scientist and author Neil Canavan writes in his gripping and timely new bookA Cure Within: Scientists Unleashing the Immune System to Kill Cancer, the way we treat cancer is about to change forever.

“This revolution – and it is precisely that – was sparked not by the invention of a new drug but by the advent of an entirely new way of thinking about and managing cancer patients,” Canavan writes. “Going forward, doctors will not use pharmaceuticals to attack a tumor, at least not directly. Rather, the oncologist will treat the patient’s immune system with a drug, thereby enabling it to track down and destroy the cancer.”

Canavan, whose book is currently being translated into Chinese, which like the U.S. is a hotbed for immunotherapy research and development, takes the reader on a compelling journey inside the once-isolated world of immunotherapy research to show the very human side of the scientists who’ve overcome unimaginable adversity to reach this plateau.

These are remarkable human beings,” Canavan, a molecular biologist and scientific advisor at The Trout Group, a New York-based investor relations firm focused on biotechnology, told The Reno Dispatch. 

“The reason these people were all so open with me is that, for years, everyone told them what they were studying was crap. What that did was get them to circle the wagons. They’re a very tight group," he said.

Summit participants included such IO pioneers as Gordon Freeman, professor of oncology at Dana Farber Cancer Institute at Harvard University, who was instrumental in the research of PD-1, and Blythe Sather, associate director of Juno Therapeutics, which was recently purchased by Celgene and is at the forefront of CAR-T research.

Others who attended and shared their insights included Scott Durum, who is chief of the cytokines and immunity section at the National Cancer Institute, which is part of the National Institutes of Health, Ling-Yang Hao, principal scientist, immunology biomarkers at Janssen R&D, and Albert J. Wong of the cancer biology program, neurosurgery at Stanford University Medical Center.

Naturally, the science of IO took center stage at the summit. But several invited cancer patients who have benefited from IO, or hope to, stole the show.

In forums and keynote speeches, cancer patients spoke with passion about what immunotherapy means to them, and how this new way of treating cancer, in which the patient’s own body is the drug, lends itself to greater involvement by the patient.

Shahzad Bhat, who’s been fighting a type of B cell lymphoma, was told last October that he had exhausted his treatment options and had just three months to live.

But neither he nor his wife Nicole Bhat accepted that prognosis. One month after he was told he was dying, Shahzad obtained referrals from three different cancer centers stating he was a candidate for Yescarta, which she learned was approved by the FDA just weeks prior to these referrals.

Nicole, who stayed on top of the immunotherapy news, presented a proposal to the couple’s insurance company showing how CAR-T is actually less expensive than long-term chemo or other treatments because unlike chemo, which can last for months, CAR-T is a one-shot treatment.

Shahzad was the first patient to be treated with Yescarta at Stanford since the drug was approved by the FDA, and just the 7th patient in the United States to be treated with Yescarta.

Just after Christmas, Shahzad’s T-cells were injected back into his body. He had only very mild cytokine release syndrome, which is typically the most severe side effect of CAR-T. There was no neurotoxicity.

When they announced during one of the patient forums at the summit that Shahzad was in complete remission, the crowd of scientists, physicians, pharma execs and other patients broke out in loud and sustained applause.

Patients Take Charge of Their Treatment, and the Conference

Several of the patients who attended the summit expressed deep gratitude for the researchers’ tireless efforts to bring these complex ideas from the lab to the clinic, and for the doctors who make the effort to learn about all the latest discoveries.

But Shahzad and Nicole and other patients who attended the conference also expressed frustrations about the sometimes-prohibitive rules that regulatory agencies impose on cancer clinical trials, the price of some drugs, and the fact that doctors are sometimes not aware of the latest treatments.

Everyone at the conference, including the oncologists in attendance, agreed this is a problem, but that it is very hard to fix because changes in immunotherapy are happening literally every day, and doctors understandably spend most of their time with patients.

During the conference’s panel discussion on “Experiences and Perspectives on Real-Life Application of Immunotherapies,” Valerie Frye, an Air Force veteran and two-time gynecological cancer survivor who lost her husband last year to colon cancer, addressed the regrettably small percentage of cancer patients who participate in immunotherapy clinical trials.

She said that if companies want more patients in their clinical trials, the designers of the trials need to stop imposing unnecessary patient requirements, such as mandating that they fail two standard-of-care therapies before being eligible for the trial.

By then, Frye explained, most patients are too sick to meet the other requirements and will not qualify.

“The pace of immunotherapy breakthroughs and personalized, targeted, precision oncology means that the standard design of clinical trials is inadequate and costing stage IV colon cancer patients their lives,” Frye told The Reno Dispatch. “Clinical trials need to be redesigned to be flexible enough to keep pace with genomic and immunological breakthroughs and stop being one size fits all."

Despite her frustration with how trials are sometimes hard to get into, Frye was pleased to attend the conference and learn about immunotherapy and the current research being done.

“Immunology is where many successful cancer cures and treatments will be developed,” she said. “I wanted to meet the front-line cancer research scientists and let them know how important their work is to us patients and caretakers, and the hope they are bringing us. I wanted to thank them.”

Frye said the scientists at the conference were surprised but pleased to see and hear from so many patients. “It was a first for many of the researchers,” she said. “I wore out my brain and Google trying to understand each lecture I attended, but I was fascinated with the topics and the presenters.”

Presiding With Benevolent Authority

The conference was put on by GTCbio, an international communication company whose CEO, Satish Medicetty, a scientist and former pharma executive, wisely brought in Kamala Maddali, a pharma exec and global patient advocate, to help shine a brighter light on the cancer patients’ perspective.

Maddali is vice president, biopharma collaborations, market development and companion diagnostics at Cancer Genetics Inc., a global company that provides complex genetic tests of patients that help physicians determine what immunotherapies to use and how to use them.

A pioneer in the movement to build bridges between patients, pharma and physicians, Maddali is more than just a patient advocate. She has made it her life’s work to bring the disparate pieces of the cancer puzzle together. She compassionately deconstructs, demystifies and humanizes the entire cancer process for all parties. And everybody wins.

“This is a fascinating time to learn and lead as a champion for patients by engaging them in the right discussions with their physicians, pharma, and innovation companies like the diagnostics and the labs,” said Maddali, who presided over the conference with benevolent authority, hosting several of the patient-focused panels and digging deep to get the most and best out of all the participants.

“Patients feel like they want to be champion of their health decisions instead of a listener and a recipient,” Maddali said after the conference,” she said.

With the advancements of social media and the internet, she added, “More and more patients are forming networks and working groups to understand better their mutual journeys and learn from their personalized experiences. Patients and their families are more informed and involved, and now we are giving a voice to patients at science forums, and in doctors' offices”

Maddali added that this approach is not only kind, it's also smart.

“Patients and their support groups are more engaged in and informed about their treatment options and their cancer than ever before, and when this happens, everybody wins,” she said.

Scientists Are People, Too

The scientists involved in immunotherapy, too, are gaining an evidently better understanding of the human element of their work.  

Mike Gresser, chief scientific officer at ImmunGene, a biopharmaceutical company north of Los Angeles, spoke at the conference about an innovative new immunotherapy he is developing called Focused Interferon Therapeutics (FIT), which enables interferon to safely treat cancer.

Interferon was a very effective cancer killer, specifically for patients with melanoma, but it was too toxic for many patients to tolerate.

But with this technology, Gessner explained, the interferon is delivered via a monoclonal antibody, which allows the patient to receive a profoundly higher dose of the drug without feeling the harsh systemic side effects.

Gessner said he was inspired to come up with more effective but less toxic and less expensive cancer treatments after his wife was diagnosed with breast cancer.  

While supporting her as she went through surgeries, chemotherapy, radiation, and endocrine therapy for her cancer, Gresser said he observed how harsh these treatments often are.

“They drain the energy and reduce the quality of life of patients, and can even have strong effects on their personalities, reducing the quality of life of those who are close to them as well as the patients' quality of life,” he said.

Gresser said he is now committed to developing cancer medicines that both increase efficacy and offer much better safety and tolerability.

“Unfortunately, in many cases cancer therapy regimens could readily qualify as cruel and unusual punishment,’ and very likely would not be legal as a penalty for criminals convicted of capital crimes. Patients should not be punished for having, through no fault of their own, cancer,” he said.

Gresser thinks two factors are very important in the patient-empowerment phenomenon that is happening in the immunotherapy sector.

One is the obvious ready availability of information accessible by on the Internet, which he said enables intelligent and motivated patients to “become experts on their disease and on approved and experimental therapies, so they are able to ask informed questions and even challenge their physicians.”

The other factor which is not as immediately obvious, he said, is the “emergence of patient advocacy groups that help inform and give hope to cancer patients, so they can participate actively with their physicians in the design of their treatment regimens.”

Powerful Patient Advocacy Group

One of the most effective and disruptive of those patient advocacy groups is COLONTOWN, a members-only Facebook for colo-rectal cancer patients whose founder, Erika Brown, a former high-powered executive, saw her life take a 180-degree turn when she was diagnosed with colon cancer.

Thanks to Brown, COLONTOWN now has more than 40 “secret” sites on Facebook and covers the gamut for patients, from information to inspiration to humor to updates on new treatments.

Brown, who brought a group of colon cancer patients to the summit, was impressed with how much emphasis the conference planners placed on the patient perspective.

“I'm very pleased to be associated at any level with the farsightedness and intelligence of a conference leader such as Satish,” Brown told The Reno Dispatch.

Many years ago, when she attended her first medical conference, Brown said, “I was told by another patient advocate in attendance that it was our job to ‘stay at the back, don’t ask any questions, don't talk to any of the docs, etc,’ because our presence as patient advocates was not really welcome. How times have changed.”

COLONTOWN’S plucky but loving spirit is embodied in member Deborah Goldberg, who was diagnosed with stage 3b colon cancer in 2014. It progressed to stage IV (metastatic) the following year.

An active member of COLONTOWN, she’s been through numerous surgeries, radiation and chemotherapy, but has not yet been treated with immunotherapy. She does not currently qualify as her tumors are not easily accessible. But she hopes that will change soon.

CONONTOWN has meant the world to Goldberg for “providing connections, information and education to empower me to be my own best advocate and help make me the CEO of my own cancer care team, which is comprised of medical oncologists, oncological surgeons, radiologists, palliative care doctors, and more.”

Goldberg said this is essential in a time where the doctor/patient relationship is shifting dramatically.

“Medical oncologists are overwhelmed by ever-expanding treatment options such as standard of care, interventional radiology treatments, immunotherapy, clinical trials, etc. Patients need to educate themselves and be a ‘student’ of their own cancer, and harness this knowledge to participate in and help steer their treatment,” Goldberg said.

CEO Puts Patients First

Jay Roberts, CEO of Cancer Genetics, Inc., which does the advanced genetic tests that are crucially important for immunotherapy patients to know what treatment will best suit them, said the patient is the central focus of his company.

While this may sound like something every CEO in the cancer realm would say, it isn’t. You actually don’t often hear this from companies that do not have direct interaction with patients.

Cancer Genetics is of course not allowed to interact directly with patients or offer any medical advice. But they are one of the several companies that support and complement pharma that are changing the patient-pharma-physician paradigm.

“One of the challenges for us is were asked to provide diagnostics at a very detailed level, and being referred to us by oncologists out in clinical care. The challenge is that providers in community-based hospitals will not fully embrace all the next-generation sequencing and our testing that allow us to think to individual patient where precision is going,” Roberts said.

The Standard of care is evolving, he added.

“More companies like ours and pharma are bringing more knowledge and insight to the care provider. And as these tests continue to improve and become better known, oncologists and pathologists will be more willing to start embracing these new technologies,” he said.

Not surprisingly, the insurance companies are not yet fully on board with all the latest immunotherapy technologies, which are coming at them with lightning speed.

“The reimbursement for these vitals tests is nowhere near where it needs to be for the patients to get the full impact of these new technologies.” Roberts said. “This is an evolving world, as the pharma industry advances therapies that are more focused on the individual patient, they will get better and better at covering these technologies.”

Roberts is a global thought leader and chairman at Driving Insights to Action (DIA), an international forum for all who are involved in drug development and life cycle management to exchange knowledge and collaborate in a neutral setting.

DIA is currently working on providing forums for patients that enable them to talk directly to regulatory authorities and drug developers.

Roberts said DIA just recently launched an advisory committee of patients to “bring collaboration of many different groups together to have a voice at the table. We are still learning how best to bring patients into the dialogue. What we do know is that pharma wants to bring the patient in, across the industry it is becoming more important.”

Doctors and Patients Are Talking Like Never Before

The oncologists at the summit were also deeply engaged and spoke openly and honestly. Dr. Preet Chaudhary, a renowned lymphoma physician and researcher at the Keck School of Medicine of USC who chairs the lymphoma research division and is chief of the blood diseases department, engaged enthusiastically with patients at the summit.

He told The Reno Dispatch in no uncertain terms that times are changing for the better for patients, and the advent of immunotherapy is a catalyst for much of this change.

“Over the years, my patients have always been interested in learning ways to enhance their immune systems to fight cancer, which has been done to some degree with homeopathic drugs. There is always a human inclination for patients to embrace an approach that is more natural, something that is immune-related versus chemo. But we physicians had very little to offer,” Chaudhary said.

In immunotherapy, he explained, the patient’s immune system essentially is the treatment, and “that is something patients intuitively understand and like that.”

Chaudhary said that for the first time in history, “We as physicians feel more confident that we can get the upper hand against a disease as terrible as cancer -- in the form of a cure, or long-term remission, or turning cancer into a chronic disease. We now have much better understanding of the molecular basis of these cancers, and we are coming up with very effective and targeted therapies.”

Chaudhary added that in his practice, the patient always comes first. That is one thing he said will never change.

“I have a simple rule. Call it a creed: The strong always protect the weak. Patients are simply unlucky, and they need protection. If you are a physician you have been given a certain amount of power, and the whole point of power is to make you less afraid. If you use your power only to hold on to that power, and you do not use it to help others, you are lost. For me, the biggest source of inspiration, every day, are the patients. “

Chaudhary, who is currently developing a CAR-T technology at USC that that he hopes will be even safer, with fewer side effects, said he wishes the public knew just how long and difficult the journey has been for CAR-T researchers to arrive at this turning point.  

“CAR-T receptors were first described in 1989, but it’s taken nearly 30 years for this concept to become a successful drug,” he said. “That entire process was painstaking, and it of course had to be funded by someone.”

Traditionally, Chaudhary said, this funding comes from NIH, which is facing the very real possibility of draconian budget cuts under the current anti-science administration.

“It’s important for the public to realize that we as a nation need to invest in fundamental research. We have a roadmap that shows us how to get to the destination, but we are running out of fuel. We need to support this research to get where we all want to go,” he said.

The Big Picture Is Not Lost

GTCbio’s CEO, Satish Medicetty, who created this summit, said the most important thing he learned from the patient-centered panels at the conference was that the physicians are “overwhelmed” with the pace of new information in the recent years and they are welcoming the partnership with patients and other resources to help them come up with the best treatment plan.

"I was moved by the self-empowerment demonstrated by patients and survivors who are helping other patients,” Satish says. “In particular, I would like to mention Nicole Bhat, who has done a tremendous job of educating herself and connecting the dots to eventually find the best and most effective treatment option for her husband, Shahzad. “

Satish said the physicians and researchers at the conference “really appreciated the participation from the patients, who will make sure that the big picture is not lost in the busy details of drug development, commercialization, and the practice of medicine.”

3 comments:

  1. Polly Matzinger started the revolution in 1994, validating William Coley's work on cancer and immune response back in the 1890's at New York Cancer Hospital (now Sloan-Kettering). The revolution started a long time ago and is sadly only being acknowledged today (minus the credit to Dr. Matzinger and Dr. Coley).

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    1. Baron, respectfully, you are conflating two very disparate things. You are referring to the scientists, who of course began this immunotherapy revolution a long time ago with Coley's Toxins, etc. But what I am referring to in the headline and in the story is the PATIENT revolution. Patient awareness of immunotherapy on any sort of broad scale is literally just beginning. Your comment here was rather curt and dismissive, whereas most folks who read this story are actually quite impressed and inspired. No offense taken, but I hope you're not a physician, 'cuz your bedside manner needs a bit of work. :)

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