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In 2012, doctors told the Whitehead family to take their 6-year-old daughter home to live her last days, as there was nothing more they could do to treat her acute lymphocytic leukemia. All conventional treatment had failed, because she was refractory to treatment, meaning that her cancer did not respond to conventional therapy. Can you imagine getting such heartbreaking news about such a young child?

However, there was one last experimental option. The Children’s Hospital of Philadelphia had successfully treated three adults with its version of CAR-T cell therapy and they invited Emily to be the first child in its clinical trials. Emily nearly died from the treatment, but ultimately survived and went into remission. Emily is now 12 years old and is still cancer-free. She participates fully in life like any other 12-year-old. The Novartis CAR-T Immunotherapy version that worked for Emily and others became the first commercial treatment approved by the FDA.

CAR-T Immunotherapy

CAR-T Immunotherapy is a treatment which optimizes the body’s ability to target, attack and kill tumor cells. On August 30, 2017, the Federal Drug Administration (FDA) approved the Novartis version of CAR-T cell therapy for children and young adults with B-cell acute lymphoblastic leukemia (ALL), which is the most common form of childhood cancer in America. While current chemotherapy, radiation and bone marrow transplants result in remission for about 80 percent of people with ALL, there are still about 20 percent who do not respond to current treatment. These individuals are said to be refractory to treatment. For them, CAR-T is a lifesaving option. However, medical miracles come at a large cost to health plans and Payors.


Tisagenlecleucel is the name of the Novartis commercial product branded as Kymriah and approved by the FDA. Since the inception of this miracle “living drug” more pharmaceutical companies have received FDA approval. Research continues on the application of CAR-T therapy to other solid tumors and second-generation refinements are beginning to evolve.

The CAR-T process begins when the doctors harvest T cells from the patient, and then manipulate the cells through genetic engineering to produce new surface proteins called chimeric antigen receptors (CARS). These modified cells are warriors that recognize and attack cancer cells. These CARS are then infused back into the patient, where they enhance and enable the immune system to target and kill cancer cells.

In December, 2014, Juno Therapeutics reported that 24 of 27 adults in its Phase 1 Trial for refractive acute ALL had been put into remission through the use of CAR-T Cell Therapy. That is astounding, since these individuals had stopped responding to any other type of treatment (American Society of Hematology (ASH 2014, Abstract 382)).  Soon thereafter, Juno Therapeutics became the largest biotech initial public offering of 2014 and the second company to get CAR-T approval. Since that time, Juno has several more CAR-T trials in progress.

Other pharmaceutical companies are also in the race. Kite Pharma is working on trials for several different cancers, as well as ways to amplify the cell’s attack abilities and moderation of the technology when adverse reactions occur. Bellicum Pharmaceuticals is working on a next generation mechanism that is called GoCAR-Ts, meaning that the co-stimulating function and the antigen recognition cell functions have a separate switch activated by the drug Rimiducid. To become fully operational, both the cancer cell and the drug must be present.

MD Anderson has been experimenting with a system called, “Sleeping Beauty,” which uses electrical current to incorporate desired elements into T cells. 

One day these therapies will not be “last resort” treatment, but a regular part of conventional therapy. For now, these therapies are granted breakthrough or “orphan drug” status from the FDA.


Safety Concerns

There have been a few deaths and adverse side effects, known as cytokine-release syndrome (CRS) which some term a “cytokine storm”. It seems that those with a greater tumor burden, infection or an underlying other disease condition are more likely to have a stronger immune response causing adverse symptoms up to and including death. Children weather the “cytokine storm” better than adults. 

Symptoms of CRS may include high fevers, aches, weakness, tachycardia, breathing difficulty, and less often, pulmonary edema and neurotoxicity (confusion, delirium, seizures, gait and balance problems), GI symptoms (vomiting, diarrhea or constipation), and changes in liver enzymes or blood cell counts. These side effects are treated symptomatically.

Significance to Health Plans and Payors

CAR-T Cell treatment is very expensive. The Novartis CAR-T drug Kymriah costs $475,000, which doesn't include the hospital expenses required when Novartis collects each patient's T-cells for re-engineering, and later, when the personalized Kymriah is administered. Gilead’s version, Yescarta, the second drug to gain FDA approval, was developed by Kite and sold to Gilead, and is more cost effective at $373,000.

The total cost of treatment is greater than the Immunotherapy, as the body must be prepared to accept the modified cells, and symptoms resulting from treatment need to be managed. Further, there is always the cost of the treatment that occurred before the individual became eligible for CAR-T Immunotherapy and the medical care for all conditions that affect each patient.

Continuing research is expected to keep reducing costs of this phenomenal therapy. For example. A French company is pioneering allogenic CAR-T therapy, where cells are collected from donors, so that cells do not have to be individually modified in a special manufacturing process. Another company in Belgium is also working in the same area of research. Celgene, like other large pharmaceutical companies, have also invested in smaller companies doing research in this area.

For the time being, insurance companies will need to screen individuals carefully to ensure that potential candidates have explored all treatment options prior to qualifying for CAR-T Therapy. One day, the cost will enable many more individuals to qualify, as it may become part of basic treatment.

When a Plan member is likely to become eligible for treatment, be sure to notify the Stop Loss Carrier and to work with the TPA and medical management team proactively.


APH Technology Delivers Cutting Edge Visibility to Clients

APH has the technology to keep clients informed about member condition status, deliver predictive modeling on treatment costs, and serve up indications that a member may be nearing the point where CAR-T is the only viable option. Staying abreast of current trends and ways to optimize member care and Plan costs are vital to managing costs in this area.

Contact APH today so that we can show you how Poindexter can support your needs in this, and other costly areas of care.