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CAR T Cell Key Points
Practical Implementation of CAR T-Cell Therapy in Lymphomas: Key Points for Advanced Practice Providers

Released: October 28, 2024

Expiration: October 27, 2025

Beth Faiman
Beth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO
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Key Takeaways
  • With the recent approvals of CAR T-cell therapy for various types of B-cell lymphomas, understanding best practices and coordination of care is critical to ensure optimal treatment.
  • Patient- and disease-specific factors, logistics, and social support are among the components that must be considered when proceeding with CAR T-cell therapy.

Currently, 4 chimeric antigen receptor (CAR) T-cell therapies are approved for different types of relapsed/refractory B-cell lymphomas—axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, and tisagenlecleucel. This commentary includes my thoughts on key questions related to treatment considerations, best practices, and care coordination with the implementation of CAR T-cell therapy for patients with lymphoma. 

Axicabtagene ciloleucel is currently FDA approved for adult patients with large B-cell lymphoma (LBCL) that is refractory to or has relapsed within 12 months of first-line chemoimmunotherapy; patients with relapsed/refractory LBCL (including diffuse large B-cell lymphoma [DLBCL] not otherwise specified, primary mediastinal LBCL, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma) after ≥2 lines of therapy; or adult patients with relapsed or refractory follicular lymphoma after ≥2 lines of systemic therapy (under accelerated approval).

Brexucabtagene autoleucel is currently FDA approved for adult patients with relapsed or refractory mantle cell lymphoma (under accelerated approval) or with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

Lisocabtagene maraleucel is currently FDA approved for multiple B-cell lymphomas, including:

  1. Patients with LBCL (including DLBCL not otherwise specified, DLBCL arising from indolent lymphoma, high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B) that is refractory to or has relapsed within 12 months of first-line chemoimmunotherapy, or those with relapse after first-line chemoimmunotherapy who are not eligible for hematopoietic stem cell transplantation, or those with relapsed or refractory disease after ≥2 lines of systemic therapy
  2. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received ≥2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor (under accelerated approval)
  3. Patients with relapsed or refractory follicular lymphoma after ≥2 lines of systemic therapy (under accelerated approval)
  4. Patients with relapsed or refractory mantle cell lymphoma (MCL) who have received ≥2 prior lines of therapy, including a BTK inhibitor

Tisagenlecleucel is currently FDA approved for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse; adult patients with relapsed or refractory LBCL after ≥2 lines of systemic therapy (including DLBCL not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma); or adult patients with relapsed or refractory follicular lymphoma after ≥2 lines of systemic therapy (under accelerated approval).

What are some considerations when evaluating a patient with lymphoma for CAR T-cell therapy?
When evaluating whether a patient would be a candidate for CAR T-cell therapy, there are several patient- and disease-specific factors that must be considered.

First, it is important to ensure that the patient meets the FDA labeled indication for a particular product. Additionally, though it may vary per product, the median manufacturing time for CAR T-cell therapy is approximately 17-28 days. From a disease standpoint, it is important to consider whether the patient can wait for treatment during that manufacturing period, or whether they need to be considered for salvage or bridging therapy until the CAR T-cell therapy is ready for infusion. The immediate prior therapy that the patient has received is important to consider as well, as it may impact the ability to harvest T-cells for CAR T-cell manufacturing.

There are many other important questions that must be asked. If the patient is receiving concomitant immunosuppressive therapy, can this be stopped prior to cell collection? What is their infectious disease history and does the patient have any active infections? From a patient standpoint, what is the status of their organ function? Are there any concerns with their ability to tolerate the treatment? What social support do they have?

If more than 1 CAR T-cell therapy is approved for a patient’s specific malignancy, how do you decide which product to use?
Certainly, the product labelling and whether it is approved for a particular patient’s malignancy is important. Some insurance companies might prefer a particular product per their formulary. Additionally, providers may have a preference based on experience and availability.

From a toxicity standpoint, lisocabtagene maraleucel tends to be gentler with regard to the risk of cytokine release syndrome, with fewer patients experiencing grade 3 or higher events. So for patients who are more frail, have comorbidities, or are elderly, lisocabtagene maraleucel may be preferable compared with axicabtagene ciloleucel. Similarly, immune effector cell–associated neurotoxicity syndrome (ICANS) tends to occur less frequently and at a lower grade with lisocabtagene maraleucel compared with axicabtagene ciloleucel, brexucabtagene autoleucel, and tisagenlecleucel.

What supportive care measures should be considered in a patient who has received or will be receiving CAR T-cell therapy?
Though it may vary per institution, we administer antiviral and Pneumocystis jirovecii pneumonia prophylaxis. Antiepileptic drugs may also be administered for at least 1 month after CAR T-cell administration to mitigate the risk of seizures associated with ICANS. My practice is not routinely administering prophylactic dexamethasone or tocilizumab to prevent cytokine release syndrome or neurological events

Following CAR T-cell therapy administration, it is common to observe a decline in immunoglobulin levels, and patients may be at increased risk of infection indefinitely. I would recommend checking IgG levels routinely during follow-up visits and starting IVIG therapy for levels <400 mg/dL.

What are key aspects of the coordination of care of patients with lymphoma receiving CAR T-cell therapy?
The road to CAR T-cell therapy is a lengthy journey for the patient. Early referrals to CAR T-cell centers and communication with referring centers is key. Once CAR T-cell therapy is deemed the optimal therapy for a particular patient, insurance authorization, consent, and patient/caregiver education is key to successful therapy.

The process of CAR T-cell administration itself includes apheresis, manufacturing, lymphodepleting chemotherapy, and finally the CAR T-cell infusion followed by extensive monitoring. Advanced practice providers can help ensure that the referring center knows when to stop the salvage or bridging therapy prior to T-cell collection. Patients require caregiver support, given the significant monitoring postinfusion, need to live near the treating center for at least 4 weeks, and have restrictions including the inability to drive for at least 8 weeks.

What are key points to communicate to patients when discussing CAR T-cell therapy?
As mentioned, the manufacturing process for CAR T-cell therapy can be lengthy. This is not a therapy that can be obtained and administered quickly. Patients may need salvage or bridging therapy to control the disease during the time it takes to get to CAR T-cell therapy. Patients receiving CAR T-cell therapy in an inpatient setting should anticipate being admitted for at least 7 days postadministration. Patient education is critical, and it is important that patients understand the extensive preparation, time, monitoring, and risks associated with CAR T-cell therapy. Patient engagement and caregiver support are key.

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