Earlier this year, the National Comprehensive Cancer Network (NCCN) released 2 sets of Guidelines for Patients® that explain the side effects of different types of immunotherapies. The new NCCN Guidelines for Patients®: Immunotherapy Side Effects included one publication focusing on chimeric antigen receptor (CAR) T-cell therapy, and a separate publication about immune checkpoint inhibitors. Both guidelines were created with support from the NCCN Foundation®.[1]

Written in easy to understand language, the two guidelines were specifically developed for patients with cancer and their caregivers, and include infographics, definitions of terms, and additional resources.[1]

CART T-cell therapy
Chimeric antigen receptor (CAR-) T-cell therapy is a type of immunotherapy known as adoptive cell therapy. As part of the therapy, physicians extract T-cells, a type of white blood cell, from the patient’s own blood, via a process called leukapheresis, to separate and collect white blood cells.  In the laboratory, scientists add artificial receptors, known as chimeric antigen receptors, to their surface of the collected T-cells. The receptor on the surface of functions as a type of “heat-seeking missile.” The modified T-cell is then enabled to produce chemicals that kill cancer. After the “manufacturing process” is completed, the CAR T-cells are infused back into a patient’s body through an IV, where they begin multiplying and attacking tumor cells. CAR-T therapy may be offered to people when their cancer comes back.

Jordan Gauthier, MD, MSc is a hematologist-oncologist at Seattle Cancer Care Alliance (SCCA) with expertise in blood cancers, bone marrow transplantation and cellular immunotherapy, about the CAR T-cell therapies, the Guidelines for Patients® and side effects of treatment. Photo courtesy: © 2020 Seattle Cancer Care Alliance (SCCA). Used with permission.

Traditional chemotherapy affects all cells and often fails to completely eradicate cancer, potentially leaving patients with long-term complications, including other forms of cancer. In contrast, CAR T-cell therapy, unlike chemotherapy, uses the immune system to target cancer. And unlike chemotherapy, which is given over multiple cycles and could go on for months or years, CAR T-cell therapy is only administered once.

The NCCN published the latest in its series of guidelines intended to inform patients and their caregivers about adverse events associated with cancer therapies.  The Guidelines for Patients are based on the NCCN Guidelines used by clinicians worldwide, which have been found to improve the likelihood of successful treatment and longer survival while also reducing costs, according to numerous independent studies. They cover every major type of cancer as well as prevention, supportive care, and specific patient populations.

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Onco’Zine spoke with Jordan Gauthier, MD, MSc, a hematologist-oncologist at Seattle Cancer Care Alliance (SCCA) with expertise in blood cancers, bone marrow transplantation and cellular immunotherapy, about the CAR T-cell therapies, the Guidelines for Patients® and side effects of treatment

Onco’Zine: What are some common side effects of CAR-T?

Jordan Gauthier: The most common side effects of CAR-T are cytokine release syndrome (CRS) and neurologic, or nervous-system related, problems together known as immune effector cell-associated neurotoxicity syndrome (ICANS). Other side effects include tumor lysis syndrome (TLS), low blood cell counts, and low numbers of B cells.

O: What is CRS and how common is it?

JG: CRS stands for cytokine release syndrome and is the most common side effect for patients who receive a CAR-T transfusion. CRS is the release of cytokine proteins that cause inflammation in the blood after a CAR-T infusion. Cytokines are proteins that carry out different immune-related jobs in the body—pro-inflammatory cytokines contribute to inflammation and anti-inflammatory cytokines help reduce it.

While most CAR-T patients experience CRS, it is not a necessary experience for CAR-T cells to work. CRS symptoms usually begin days after infusion and come in the form of fever, chills, rapid heartbeat, trouble breathing, low oxygen and low blood pressure. Most patients who experience CRS have mild cases that last for a week.

O: What key information about CAR-T side effects was shared in the recently published NCCN guidelines?

JG: In addition to CAR-T-cell therapy benefits, the recently published NCCN guidelines address the most common side effects as well as their symptoms. The NCCN guidelines are based on the same treatment information doctors use and help patients talk about the best options for treating diseases.

As a new type of immunotherapy, CAR-T sets out to find and bind to cancer cells, essentially killing them. The guidelines not only explain common side effects and symptoms, they detail the steps hospitals, clinics and doctors can and should take to treat them. For example, patients may receive medication to prevent seizures before receiving CAR-T-cell therapy, and immunoglobulin replacement therapy may be used to strengthen the immune system and fight infection after CAR-T infusion.

Furthermore, the guidelines make special note of treatments for the most common side effects should they occur, such as tocilizumab for CRS, and intravenous corticosteroid therapy to treat CRS and ICANS.

O: How should clinicians adapt cancer treatment based on these guidelines?

JG: These guidelines are fairly comprehensive, and it is my thought that clinicians can use them as a guide to have thoughtful conversations with their patients. I also believe that they will be updated quite frequently because this is still early days for these new treatments.

Currently, there are only three products approved by the FDA and only two that are most commonly prescribed for use in adult patients. It is important to note that we are still learning and when we have more data we will be able to further define these guidelines for both clinicians and patients.

O: What do these guidelines mean for patients?

JG: The guidelines provide potential patients with necessary information on CAR-T-cell therapy, which helps to inform their conversations with doctors and make the best decision for treatment.

[1] National Comprehensive Cancer Network. NCCN Guidelines for Patients®: Immunotherapy Side Effects—CAR T-Cell Therapy (2020). Last accessed on August 11, 2020. [Download]
[2] National Comprehensive Cancer Network. NCCN Guidelines for Patients®: Immunotherapy Side Effects Immune Checkpoint Inhibitors (2020). Last accessed on August 11, 2020. [Download]

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