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The Dawning of a New Era

The Dawning of a New Era

by Alice Jamba, VP of Clinical Services, Advanced Medical Strategies

On August 30, 2017, the FDA granted US approval to Kymriah (tisagenlecleucel), the first therapy based on gene transfer. Engineered chimeric antigen receptor T cell (CAR-T) treatment technology is designed to harness the power of a patient’s own immune system to effectively target and kill cancer cells. Approved to treat B-cell refractory/relapse Acute Lymphoid Leukemia* (ALL), Kymriah is an innovative immunocellular therapy produced by pharmaceutical company Novartis. For some patients with resistant disease Kymriah could prove to be a last hope, life-saving therapy. FDA commissioner Scott Gottlieb has said the medical community is “entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer.”

How it works: T cells are critical to the immune system’s ability to detect and kill cancer cells. However, the immune system is unable to kill cancer cells when tumor-specific T cells are deficient in number, unable to function properly, or fail to recognize cancer as foreign to the body. Kymriah is made of re-engineered T cells collected from each patient. A blood sample is taken, frozen, and forwarded to Novartis. It takes 3-4 weeks to manufacture Kymriah, which will then be re-infused into the patient.

Collect patient’s white blood cells

Isolate and activate T cells

Grow and expand number of T cells

Infuse patient with engineered T cells

 

Novartis has stated that it designed a manufacturing and supply chain platform that can allow for individualized treatments on a global scale. Currently, there are 20 administration locations in the US prepared to deliver therapy. By the end of 2017, there is expected to be 32 centers in total.

Qualification for treatment: For use in children and young adult patients under age 25 years with refractory disease or have relapsed at least twice. Patients meeting criteria will have likely received multi-modality treatment including chemotherapy, radiation, targeted therapy or stem cell transplant. Less than 10% of these patients survive 5 years.

Treatment initiation: The expectation is that the harvesting of T cells will begin within days of approval. (Carriers will likely receive requests with claims in the immediate future.)

Pre-Treatment: Pre-medicate with lymphodepleting chemotherapy regimen of Fludara and Cytoxan.

Dosing: Kymriah is a one-time only therapy. Dosing is weight based using a 2-tiered method. It is given 2-14 days after completion of Fludara/Cytoxan regimen. Kymriah is administered through a routine intravenous line—it takes about one hour. Please refer to PredictRx for the specific dosing regimen.

Post-Treatment/Complications: The patient needs to be within 2 hours of the administering facility for at least 4 weeks post infusion. The most common adverse reactions are cytokine release syndrome** (CRS), low gamma globulin, infections-pathogen unspecified, fever, decreased appetite, headache, encephalopathy, low blood pressure bleeding episodes, fast heart rate, nausea, diarrhea, vomiting, viral infectious disorders, low oxygen level, fatigue, acute kidney injury and delirium.

Pricing: The Wholesale Acquisition Cost (WAC) for Kymriah is $475,000 for a one-time treatment. Novartis says it will only collect payments from CMS when patients respond to treatment by the end of the first month.

Novartis plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA), for the treatment of adult patients with refractory or relapsed diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.

 

*ALL: Acute Lymphocytic/Lymphoblastic Leukemia is a cancer of the lymphocytes, a type of white blood cell involved in the body’s immune system. Abnormal cells crowd other cells in the bone marrow, preventing the production of red blood cells (which carry oxygen), other types of white blood cells and platelets (parts of the blood needed for clotting). As a result, those with ALL may be anemic, more likely to get infections and bruise or bleed easily. ALL comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US—please consult PredictDx for more specifics of this, and all other, medical diagnoses.

**Cytokine release syndrome (CRS): 49% of patients treated with Kymriah experienced grade 3 or 4 CRS, an on-target effect of the treatment that may occur when the engineered cells become activated in the patient’s body. Actemra (tocilizumab) is approved to treat CAR T cell-induced CRS and should be readily available at time of infusion—please consult PredictRx for this, and all other, specific drug dosing regimens.

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