Who is CAR-T For?
CAR-T currently treats some aggressive subtypes of lymphoma. In addition to subtype and stage, physicians will also assess the patient’s overall health, fitness and circumstance for this treatment. This may include the patient’s comorbidities, the associated ability to withstand the vigorous treatment, and their willingness and ability to travel for treatment. There are specific eligibility criteria for each CAR-T therapy, based on what was learned in clinical trials and regulatory approvals.
Generally speaking, the following patients are eligible for CAR-T therapy:
- Were diagnosed with a subtype of lymphoma for which the CAR-T therapy is approved
- Meet regulatory criteria (e.g. relapsed twice and have been previously treated)
- Have tumours that express the specific antigen the therapy targets
- Satisfactory organ function and performance status
- No active infections
- No significant cardiac, neurological or immune dysfunction
Physicians will discuss patient’s eligibility and will send relevant medical records to the specialty cancer
centre that performs the CAR-T therapy to be evaluated for treatment.
Understanding patient outcomes after treatment with CAR-T therapy is important because while the initial results for some patients are positive, clinical effectiveness varies considerably amongst patients. The ideal patient candidate is still under trial. Some patients achieve long-term durable remission, but CAR-T therapy is not currently considered a cure as more data is needed to see if patients who achieve a full remission stay disease-free long-term. Currently available 4-year survival data for DLBCL patients shows promising results thus far.
The outcomes measured in clinical trials include:
Complete response rate (CR)
- The percentage of patients who respond to treatment with the disappearance of all signs of cancer. Even if patients do not achieve CR, they could experience a partial response (PR). Overall response rate (ORR) is the sum of CR and PR.
Median overall survival (mOS)
- The median length of time from the date of diagnosis or the start of treatment that patients are still alive.
Progression-free survival (PFS)
- The length of time during and after treatment that a patient lives with disease but it does not progress or get worse.
There are several short- and long-term side effects related to CAR-T therapy. Patients are advised to stay near their treatment centre for a few weeks. Most short-term side effects can be managed with supportive therapies. However other side effects can be more serious and potentially life-threatening and may require treatment in a hospital intensive care unit.
Cytokine Release Syndrome
As CAR-T cells are released and multiply in the patient’s body, their immune system is highly activated and releases a massive number of inflammatory cytokines into the blood, causing cytokine release syndrome (CSR). This can happen within the first week after infusion or later in some cases.
The duration and intensity of CSR can vary. Some patients only experiencing mild flu-like symptoms while others have high fevers, hypoxia (oxygen deficiency), low blood pressure and multi-organ toxicity.
Neurotoxicity (now termed IEC-associated neurotoxicity syndrome or ICANS)
IEC refers to Immune Effector Cells. The CAR-T cells can have an effect on the patient’s brain, which can cause confusion, agitation and a lack of awareness. Patients may experience headaches, difficulties with written or spoken language, anxiety and occasional seizures.
Neurotoxicity can occur with or without cytokine release syndrome. If a patient also experiences CRS, neurologic symptoms more commonly occur after CRS. It is reversible in most cases, but in rare cases, cerebral oedema associated with neurotoxicity may develop, which is potentially fatal.
The severe inflammation of the immune system, which can cause multi-organ failure.
An abnormal decrease in the number of certain white blood cells in the blood coupled with fever.
B Cell Aplasia
Low number of B cells or no B cells.
A condition in which the number of red blood cells is below normal.
A decrease in the number of platelets in the blood.
A reduction in all types of gamma globulins, including antibodies that help fight infection.
Severe side effects are often the result of the high activity of the immune system brought on by the CAR-T therapy. Immunosuppressive drugs and corticosteroids are used in symptom management, with the goal of curtailing the side effects without removing the CAR-T cells completely.
It is important patients and caregivers can identify symptoms quickly so they can be treated appropriately, especially since the symptoms of some side effects (like neurotoxicity) are the same as those of other medical conditions which are treated very differently.
How to Access CAR-T Therapy and Existing Challenges