PHILADELPHIA When doctors saw the report on Bill Ludwigs bone-marrow biopsy, they thought it was a mistake and ordered the test repeated. But the results came back the same: His lethal leukemia had been wiped out by an experimental treatment never before used in humans.
We were hoping for a little improvement, remembered the 72-year-old retired New Jersey corrections officer, who had battled the disease for a decade. He and his oncologist both broke down when she delivered the good news in 2010. Nobody was hoping for zero cancer.
The pioneering therapy administered to Ludwig and a few other adults at the University of Pennsylvania hospital paved the way for clinical trials with children. Six-year-old Emily Whitehead, who was near death, became the first pediatric recipient in 2012. Like Ludwig, she remains cancer-free.
Such results are why the treatment is on track to become the first gene therapy approved by the Food and Drug Administration. An FDA advisory committee will decide Wednesday whether to recommend approval of the approach, which uses patients own genetically altered immune cells to fight blood cancers.
If the panel gives the nod, the agency probably will follow suit by the end of September. That would open the latest chapter in immunotherapy a true living drug, said Penn scientist Carl June, who led its development.
The CAR T-cell treatment, manufactured by the drug company Novartis, initially would be available only for the small number of children and young adults whose leukemia does not respond to standard care. Those patients typically have a grim prognosis, but in the pivotal trial testing the therapy in almost a dozen countries, 83percent of patients went into remission. A year later, two-thirds remained so.
And childhood leukemia is just the start for a field that has attracted intense interest in academia and industry. Kite Pharma of Santa Monica, Calif., has applied for FDA approval to treat aggressive non-Hodgkins lymphoma, and a similar Novartis application is close behind. Researchers also are exploring CAR T-cell therapys use for multiple myeloma and chronic lymphocytic leukemia, the disease that afflicted Ludwig. They are also tackling a far more difficult challenge using the therapy for solid tumors in the lungs or brain, for example.
The excitement among doctors and researchers is palpable. Were saving patients who three or four years ago we were at our wits end trying to keep alive, said Stephen Schuster, the Penn oncologist who is leading a Novartis lymphoma study. That study and a Kite trial have shown that the treatment can put about one-third of adults with advanced disease those who have exhausted all options into remission.
Yet along with the enthusiasm come pressing questions about safety, cost and the complexity of the procedure.
It involves extracting white blood cells called T cells the foot soldiers of the immune system from a patients blood, freezing them and sending them to Novartiss sprawling manufacturing plant in Morris Plains, N.J. There, a crippled HIV fragment is used to genetically modify the T cells so they can find and attack the cancer. The cells then are refrozen and sent back to be infused into the patient.
Once inside the persons body, the T-cell army multiplies astronomically.
Novartis has not disclosed the price for its therapy, but analysts are predicting $300,000 to $600,000 for a one-time infusion. Brad Loncar, whose investment fund focuses on companies that develop immunotherapy treatments, hopes the cost does not prompt a backlash. CAR-T is not the EpiPen, he said. This is truly pushing the envelope and at the cutting edge of science.
The biggest concerns, however, center on safety. The revved-up immune system becomes a potent cancer-fighting agent but also a dangerous threat to the patient. Serious side effects abound, raising concerns about broad use.
Treating patients safely is the heart of the rollout, said Stephan Grupp of Childrens Hospital of Philadelphia, who as director of the hospitals cancer immunotherapy program led early pediatric studies as well as Novartiss global trial. The efficacy takes care of itself, but safety takes a lot of attention.
One of the most common side effects is called cytokine release syndrome, which causes high fever and flulike symptoms that in some cases can be so dangerous that the patient ends up in intensive care. The other major worry is neurotoxicity, which can result in temporary confusion or potentially fatal brain swelling. Juno Therapeutics, a biotech firm in Seattle, shut down one of its CAR T-cell programs after five patients died of brain swelling. Novartis has not seen brain swelling in its trials, company officials said.
To try to ensure patient safety, Novartis is not planning a typical product rollout, with a drug pushed as widely and aggressively as possible. The company instead will designate 30to 35 medical centers to administer the treatment. Many of them took part in the clinical trial, and all have gotten extensive training by Grupp and others.
Grupp said he and his staff learned about the side effects of CAR T-cell therapy and what to do about them through terrifying experiences that began five years ago with Emily Whitehead.
The young girl, who had relapsed twice on conventional treatments for acute lymphoblastic leukemia, was in grave condition. Grupp suggested to her parents that she be the first child to get the experimental therapy.
I said, Surely, this has been tried on kids somewhere else in the world, recalled her father, Thomas Whitehead of Philipsburg, Pa. But Steve said, Nope, some adults got it, but that was a different kind of leukemia.
After she received the therapy, Emilys fever soared, her blood pressure plummeted, and she ended up in a coma and on a ventilator for two weeks in the hospitals intensive care unit. Convinced his patient would not survive another day, a frantic Grupp got rushed lab results that suggested a surge of the protein Interleukin 6 was causing her immune system to relentlessly hammer her body. Doctors decided to give Emily an immunosuppressant drug called tocilizumab.
She was dramatically better within hours. She woke up the next day, her seventh birthday. Tests showed her cancer was gone.
The approval of CAR T-cell therapy would represent the second big immunotherapy advance in less than a decade. In 2011, the FDA cleared the first agent in a new class of drugs called checkpoint inhibitors. It has approved five more since then.
There are big differences between the two approaches. The checkpoint inhibitors are targeted at solid tumors, such as advanced melanoma and lung and bladder cancer, while CAR T-cell therapy has been aimed at blood disorders. And although checkpoint inhibitors are off the shelf, with every patient getting the same drug, CAR T-cell therapy is customized to an individual. Many immunotherapy experts think the greatest progress against cancer will be achieved when researchers figure out how to combine the approaches.
For the Penn team, the CAR T-cell story goes back decades, starting at the then-National Naval Medical Center in Bethesda, Md., where June and a postdoctorate fellow named Bruce Levine worked on new HIV treatments. In the process, they figured out a way to turbocharge T cells to make them more powerful and plentiful.
The pair moved to Philadelphia in 1999 and dove into cancer research. Two years later, Junes wife died of ovarian cancer, something he has credited as spurring him to work even harder in the field. In the years that followed, researchers across the country, including at the Memorial Sloan Kettering Cancer Center in New York and Fred Hutchinson Cancer Research Center in Seattle, racked up an array of tantalizing discoveries involving T cells.
Fast-forward to 2010, when Ludwig, who lives in Bridgeton, N.J., became Penns first patient to receive CAR T-cell therapy. Two other men got the treatment not long after. One is still in remission; the other relapsed and died.
But after those three patients, the Penn researchers ran out of money for more treatments. To try to raise interest and funding, they decided to publish the results of their work. The article that appeared in the New England Journal of Medicine in August 2011 created a firestorm, June said one that brought them new resources. David Porter, a Penn oncologist working with June, was on vacation in western Maryland and had to stop at a Kohls to buy a dress shirt for the immediate TV interviews.
The pediatric trial opened the following spring with Emily. Six months later, Penn licensed its technology to Novartis in exchange for financial support, which included a new on-campus cell-manufacturing facility.
With FDA approval seeming imminent, the researchers who were so instrumental in the therapys development and testing are almost giddy. Grupp is especially pleased that the advance will be available first to children. Usually everything is developed first for adults, he noted recently, and children are an afterthought.
Read more:
This is not the end: Using immunotherapy and a genetic glitch to give cancer patients hope
This 8-year-old is free of cancer for now after a breakthrough treatment
For a 6-year-old with cancer, a future staked on medicines hottest field
Read the rest here:
First gene therapy 'a true living drug' on the cusp of FDA ... - Washington Post
- Goodie Mob - Cell Therapy Instrumental [Last Updated On: April 2nd, 2011] [Originally Added On: April 2nd, 2011]
- Dogged by pain -- stem cell therapy for dogs [Last Updated On: April 3rd, 2011] [Originally Added On: April 3rd, 2011]
- SIRA: Could Stem Cell Therapy Renew Your Body Cells? – Affordable ... [Last Updated On: April 22nd, 2011] [Originally Added On: April 22nd, 2011]
- SIRA: Could Stem Cell Therapy Renew Your Body Cells? [Last Updated On: April 22nd, 2011] [Originally Added On: April 22nd, 2011]
- Stem Cell Therapy for Kidney Failure [Last Updated On: May 13th, 2011] [Originally Added On: May 13th, 2011]
- Dogs now getting stem cell therapy [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Goodie Mob - Cell Therapy Official Music Video (VJ CodyDietz.com ReMiX) [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Stem Cell Therapy for Autism [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Dog Undergoes Stem Cell Therapy [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Stem Cell Therapy for Cerebral Palsy [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- Stem Cell Therapy for Type II Diabetes [Last Updated On: May 31st, 2011] [Originally Added On: May 31st, 2011]
- Stem Cell Therapy Success [Last Updated On: May 31st, 2011] [Originally Added On: May 31st, 2011]
- Heart Failure Patient After Adult Stem Cell Therapy [Last Updated On: June 1st, 2011] [Originally Added On: June 1st, 2011]
- Stem Cell Therapy for Rheumatoid Arthritis [Last Updated On: June 3rd, 2011] [Originally Added On: June 3rd, 2011]
- Stem Cell Therapy for Critical Limb Ischemia [Last Updated On: June 12th, 2011] [Originally Added On: June 12th, 2011]
- Stem Cell Therapy Cream: Less Wrinkles In 30 Days or Less Anti-Wrinkle Cream That Works [Last Updated On: June 12th, 2011] [Originally Added On: June 12th, 2011]
- Stem Cell Therapy for Multiple Sclerosis [Last Updated On: June 13th, 2011] [Originally Added On: June 13th, 2011]
- Clinical Advances in Adult Stem Cell Therapy: Dr. Jorge Paz [Last Updated On: June 17th, 2011] [Originally Added On: June 17th, 2011]
- Stem Cell Injection Treatment - Stem Cell Therapy [Last Updated On: June 21st, 2011] [Originally Added On: June 21st, 2011]
- Stem Cell Therapy for Spinal Cord Injury - Injured Airline Pilot Flies Again [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- Documentary: Stem Cell Therapy for Muscular Dystrophy - Ryan Benton's Story [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- Documentary: Stem Cell Therapy for Muscular Dystrophy - Ryan Benton's Story [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- XCell-Center Stem Cell Therapy Christmas Video 2010 [Last Updated On: July 2nd, 2011] [Originally Added On: July 2nd, 2011]
- Stem Cell Therapy for Stroke - Gary Steinberg, Stanford University [Last Updated On: July 9th, 2011] [Originally Added On: July 9th, 2011]
- Stem Cell Therapy Injections [Last Updated On: July 9th, 2011] [Originally Added On: July 9th, 2011]
- Stem Cell Therapy MS: Sam Harrell and The Superbowl [Last Updated On: July 13th, 2011] [Originally Added On: July 13th, 2011]
- Adult Stem Cell Therapy Clinical Advances - Dr. Jorge Paz in San Diego, CA March 2011 [Last Updated On: July 14th, 2011] [Originally Added On: July 14th, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Rationale [Last Updated On: July 15th, 2011] [Originally Added On: July 15th, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Rationale [Last Updated On: July 15th, 2011] [Originally Added On: July 15th, 2011]
- Stem Cell Therapy--Hillcrest Animal Hospital [Last Updated On: July 18th, 2011] [Originally Added On: July 18th, 2011]
- Regenerative Medicine With Stem Cell Therapy Injections at an Arizona pain clinic (602) 507-6550 [Last Updated On: July 19th, 2011] [Originally Added On: July 19th, 2011]
- Bone Marrow Aspiration - Stem Cell Therapy [Last Updated On: July 19th, 2011] [Originally Added On: July 19th, 2011]
- The New World of Medicine: Stem Cell Therapy [Last Updated On: July 29th, 2011] [Originally Added On: July 29th, 2011]
- Post Stem Cell Therapy Video for Cerebral Palsy [Last Updated On: August 3rd, 2011] [Originally Added On: August 3rd, 2011]
- Lou Gehrig's Disease (ALS): Stem Cell Therapy - A Patient's Perspective [Last Updated On: August 5th, 2011] [Originally Added On: August 5th, 2011]
- Lou Gehrig's Disease (ALS): Stem Cell Therapy - A Patient's Perspective [Last Updated On: August 5th, 2011] [Originally Added On: August 5th, 2011]
- Stroke Victim Improved With Stem Cell Therapy. More at http://www.stemcellfusion.com [Last Updated On: August 9th, 2011] [Originally Added On: August 9th, 2011]
- WAVE3 News Adipose Stem Cell Therapy [Last Updated On: August 14th, 2011] [Originally Added On: August 14th, 2011]
- Embryonic stem cell therapy in China (www.esctherapy.com) [Last Updated On: August 17th, 2011] [Originally Added On: August 17th, 2011]
- Ying Liu discusses IPS cell therapy for ALS [Last Updated On: August 17th, 2011] [Originally Added On: August 17th, 2011]
- KO Clancy [Last Updated On: August 24th, 2011] [Originally Added On: August 24th, 2011]
- Stem cell therapy in Guatemala - (closer than China) [Last Updated On: August 26th, 2011] [Originally Added On: August 26th, 2011]
- ATP Cell Therapy [Last Updated On: August 27th, 2011] [Originally Added On: August 27th, 2011]
- Dr. Craig Saunders Adult Stem Cell Therapy [Last Updated On: August 28th, 2011] [Originally Added On: August 28th, 2011]
- Spinal Cord Injury - Stem Cell Therapy [Last Updated On: August 29th, 2011] [Originally Added On: August 29th, 2011]
- Stem Cell Therapy For Alzheimer's/Dementia [Last Updated On: September 13th, 2011] [Originally Added On: September 13th, 2011]
- Stem Cell Therapy For Alzheimer's/Dementia [Last Updated On: September 13th, 2011] [Originally Added On: September 13th, 2011]
- Stem Cell Therapy (Regenerative Medicine) in New Jersey [Last Updated On: September 17th, 2011] [Originally Added On: September 17th, 2011]
- Clinical Advances in Adult Stem Cell Therapy - Dr. Jorge Paz Rodriguez (Miami) [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- Stem Cell Therapy Skin Repair and Anti-Wrinkle Cream [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- Cardiac Stem Cell Therapy [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- Adult Stem Cell Therapy for Multiple Sclerosis [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- SENS5 - Cellular Therapy for Intestinal Regeneration [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- channel 10 news stem cell therapy for hair loss part 2.flv [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- Multiple Sclerosis Stem Cell Therapy News Coverage [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- Stem-Cell-Therapy-in-China.wmv [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Adickes: Stem cell therapy [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Don Reed: Why we need new stem cell therapies and how you can help [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Repair Your Joint Injuries With Stem Cell Therapy | Los Angeles | Beverly Hills | Hollywood [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Repair Your Joint Injuries With Stem Cell Therapy | Los Angeles | Beverly Hills | Hollywood [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Ovation Cell Therapy Review (request) [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Glazer's Edge: Peyton's Stem Cells [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Glazer's Edge: Peyton's Stem Cells [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- The Spinal Cord Journey - Stem cell therapy stories from three spinal cord injury patients [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Goodie Mob - Cell Therapy - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Randolph veterinarian uses new stem cell therapy on ailing pets - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Stem Cell Therapy for Autism - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- 1 month after using Ovation Hair Cell Therapy and the results are...... - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Stem Cell Series: Part 1 - Video [Last Updated On: October 15th, 2011] [Originally Added On: October 15th, 2011]
- Stem Cell Therapy for Multiple Sclerosis (MS patient) - Video [Last Updated On: October 15th, 2011] [Originally Added On: October 15th, 2011]
- Affordable Stem Cell Therapy in Guatemala (2hrs from Miami) - Video [Last Updated On: October 16th, 2011] [Originally Added On: October 16th, 2011]
- Duffy Update, Post Stem Cell Therapy - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- Duffy Gets Stem Cell Therapy - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- Adult Stem Cell Therapy for Congestive Heart Failure [Last Updated On: October 20th, 2011] [Originally Added On: October 20th, 2011]
- CELL THERAPY - Video [Last Updated On: October 23rd, 2011] [Originally Added On: October 23rd, 2011]
- Stem Cell Therapy in Cardiac Disease - Video [Last Updated On: October 25th, 2011] [Originally Added On: October 25th, 2011]
- Stem Cell Therapy for Rheumatoid Arthritis - Community Outreach Dallas - Darnell Morris - Video [Last Updated On: October 25th, 2011] [Originally Added On: October 25th, 2011]
- UMBILICAL CORD STEM CELL THERAPY - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- Stem Cell Therapy for Multiple Sclerosis Stimulates IDO - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- Goodie Mob - Cell Therapy ( Killuminati Music ) - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]