Is there an age limit for CAR-T treatment? Can children also receive CAR-T therapy?
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Theoretically, CAR-T cell therapy can be given at any age, including children or older adults, as long as the patient has good organ function and can tolerate the toxic side effects. 2017 saw the FDA approval of Novartis’ CAR-T cell product Kymriah™ (Tisagenlecleucel) for the treatment of children and young adults (2 to 25 years old) with B-cell acute lymphoblastic leukemia patients.
The clinical use of CAR-T cells for acute leukemia in China is also high in children.
But because domestic CAR-T cell therapy is now in the clinical trial stage, different clinical trials have different enrollment requirements or age restrictions, so please consult with the clinical trial investigators.
What are the contraindications to CAR-T therapy? Can patients with lung disease, liver or kidney disease, or heart disease receive CAR-T therapy?
Contraindications to CAR-T cell therapy are:
- Patients with a prior history of epilepsy or other central nervous system disease;
- People with a graft-versus-host reaction requiring long-term immunosuppression;
- Patients with a previous prolonged QT period or severe cardiac disease;
- Pregnant or lactating women;
- Uncured patients with active infection;
- Patients with active hepatitis B or C virus infection;
- Patients with active hepatitis B or C virus infection;
- Combined use of systemic steroids within 2 weeks prior to enrollment (except for recent or current use of inhaled steroids).
In the clinical trial of CAR-T cells at our center (Department of Hematology, Tongji Hospital, Shanghai, China), the assessment of the subjects’ organ function is relatively more demanding because of the higher percentage of severe cytokine storms that occur during the treatment of acute lymphoblastic leukemia (ALL) with CAR-T cells. The assessment of each organ function is more demanding. In contrast, lymphoma patients have a lower rate of serious side effects and therefore require a more relaxed assessment of organ function. In patients with pulmonary, hepatic or renal disease or cardiac disease, CAR-T is acceptable as long as the lung function is normal and there are no occupying lesions; the liver and kidney function are normal; and the heart EF is ≥0.5 and there is no serious cardiac disease.
Current domestic CAR-T clinical trials are for advanced/refractory/resistant patients; can early or mid-stage patients be treated with CAR-T earlier?
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The current clinical application is CAR-T19 for patients with refractory relapsed B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin’s lymphoma. Because domestic CAR-T cell therapy is now in the clinical trial study phase, the enrollment requirements are relatively high, requiring patients with fair general condition, good liver, kidney, and heart function, etc.
In addition, given that CAR-T cell therapy can also lead to toxic side effects such as cytokine storm, patients with advanced tumors who have had repeated chemotherapy often have poor organ function and comorbidities that are often not tolerated, and patients with poor immune cell function are deprived of the opportunity to receive CAR-T cell therapy. Thus, in cases of poor outcomes despite receiving 1 to 2 second-line chemotherapy regimens, oncology patients should be considered for clinical trials of CAR-T cell therapy as early as possible.
On the other hand, for patients at high risk or with adverse genetic factors, who are often ineffective or resistant to chemotherapeutic agents and have rapid disease progression, the greatest benefit of CAR-T cell therapy can overcome the impact of these adverse factors on outcome. For these patients, it is even more important to consider moving the CAR-T treatment forward and enrolling in a CAR-T cell clinical trial as early as possible after first-line therapy has failed.
Is it necessary to store peripheral blood for later use in patients with hematologic tumors who have achieved complete remission?
Patients with hematologic tumors in complete remission often have to store peripheral blood for later use.
In the clinic, we often see patients with hematologic tumors whose disease has relapsed and progressed too quickly to wait for CAR-T cell preparation, or whose chemotherapy interval is too short to allow cell collection and thus lose the opportunity to receive CAR-T cell therapy. Therefore, it is recommended that patients with B-cell hematologic tumors at risk of relapse should consider storing peripheral blood mononuclear cells in advance for later use.