The evidence-based recommendations described below outline the standard follow-up procedures for CAR T-cell Therapy and are intended to assist you in providing optimal cancer follow-up care for your patient; these recommendations are not intended to be a substitute for clinical judgement.
Surveillance Activities & Timelines
The following tests should be performed as part of the minimum recommended follow-up:
- CBC, creatinine, liver enzymes, LDH, quantitative immunoglobulins should be measured every 1-3 months for the first 1-2 years after CAR T-cell therapy
- CD4 count should be measured at a minimum of 1 year after CAR T-cell therapy
- Peripheral blood flow cytometry immunodeficiency panel should be done at least every 3 months for patients with B-ALL to monitor for loss of B-cell aplasia
- Long-term survivors should have CBC measured every 6-12 months and age-appropriate cancer screening performed
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Referrals for Recurrence
Patients presenting with any symptoms or signs of recurrence should be investigated and referred back to the treating oncologist. If the oncologist's contact information is not available, search “cancer” in the Alberta Referral Directory for the most up-to-date information and instructions for referral.
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Complications & Late Effects of Treatment
| Complication |
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| Neurotoxicity |
- Rare cases of late onset immune effector cell-associated neurotoxicity syndrome (ICANS) have been reported months after CAR T-cell therapy. Consider neuroimaging and lumbar puncture to exclude other causes.
- Atypical cases of neurotoxicity such as parkinsonism, cranial nerve palsies, and neuropathy have been observed after BCMA-directed CAR T-cell therapy.
- Treatment of neurotoxicity should be done in conjunction with the CAR T-cell physician.
- Deconditioning and steroid-induced myopathy may also occur after cytokine release syndrome (CRS) and ICANS and affected patients may benefit from rehabilitation.
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| Infections |
- Late infections are the leading cause of non-relapse mortality after CAR T-cell therapy, often due to effects of prior treatment, prolonged B-cell aplasia, and delayed T-cell reconstitution.
- PJP prophylaxis with sulfamethoxazole/trimethoprim (or dapsone + penicillin if intolerant) should be continued for at least 1 year after CAR T-cell therapy and until CD4 count >200.
- HSZ/VZV prophylaxis with valacyclovir should be continued for 2 years after CAR T-cell therapy but stopped the day before the live VZV immunization is administered, with the exception of previous autotransplant recipients for whom valacyclovir may be stopped 1 month after the second non-live Shingrix immunization
- HBV prophylaxis for eligible patients should be continued for >1-2 years after CAR T-cell therapy
- Antimould prophylaxis should be considered for patients with prolonged neutropenia.
- Influenza vaccine and a complete COVID-19 revaccination series are recommended as soon as 3 months after CAR T-cell therapy.
- Other non-live immunizations are recommended starting 6 months post CAR T-cell therapy and live immunizations starting at 2 years, as per the ABMTP Standard Practice Manual recommendations for autotransplant recipients (if prior autotransplant before CAR-T) or allotransplant recipients (if no prior autotransplant): Alberta Bone Marrow and Blood Cell Transplant Program: Standard Practice Manual
- IVIg replacement is recommended for patients with recurrent and/or severe infections in the setting of hypogammaglobulinemia.
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| Cytopenias |
- Prolonged cytopenias are relatively common after CAR T-cell therapy and may take months to resolve in some cases.
- Bone marrow aspirate and biopsy should be performed for severe and/or prolonged cytopenias lasting >1-3 months to rule out disease recurrence, HLH, or MDS/AML.
- Immune effector cell-associated hematotoxicity can usually be managed with supportive care including transfusions, growth factors (EPO, G-CSF, TPO), and prophylactic antimicrobials.
- Autologous stem cell boost can be considered if available, while allogeneic stem cell transplantation is considered a treatment of last resort
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| New Malignancies |
- CAR T-cell therapy recipients should have regular CBC and age-appropriate cancer screening performed to monitor for MDS/AML and other malignancies relating to the cumulative effects of prior cancer treatment.
- Monitoring is also required for the small potential risk of secondary malignancies arising from insertional oncogenesis.
- New malignancies after CAR T-cell therapy should be reported to the cell therapy centre.
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| Psychological Distress |
- CAR T-cell therapy recipients may experience psychosocial distress related to their disease and treatment journey and should receive appropriate mental health screening and support.
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| Infertility |
- The impact of CAR T-cell therapy on fertility and the developing fetus are not yet well understood.
- Effective contraception is recommended for >6-12 months after lymphodepleting chemotherapy and CAR T-cell therapy.
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| Organ Dysfunction |
- CAR T-cell therapy recipients may be at increased risk of organ dysfunction due to the effects of prior chemotherapy, radiation, or transplantation, and monitoring and supportive care should follow relevant treatment guidelines.
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| Autoimmunity |
- Rare cases of autoimmune complications have been reported after CAR T-cell therapy, including graft-versus-host disease among prior allotransplant recipients, and should be managed in accordance with standard treatment guidelines
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Physician Support
The following resources provide support and information for physicians:
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Note: The information on this page was adapted from the AHS Guideline Resource Unit’s CAR T-cell Therapy Transfer of Care Physician Letter.
