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Navigating CAR T-Cell Therapy for MM
Navigating CAR T-Cell Therapy for Multiple Myeloma: Challenges, Patient Concerns, and Best Practices for Advanced Practice Providers

Released: February 10, 2025

Expiration: February 09, 2026

Beth Faiman
Beth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO
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Key Takeaways
  • It is important for healthcare professionals to discuss the logistics and risks of CAR T-cell therapy with their patients, ensuring they understand what to expect and addressing their concerns before beginning treatment.
  • Early patient referrals to treatment centers are crucial for optimizing patient outcomes and access to CAR T-cell therapy.

In most cases, multiple myeloma (MM) cannot be cured, but it can be treated, and chimeric antigen receptor (CAR) T-cell therapy has proven to be an effective treatment option in the relapsed or refractory (R/R) setting. Currently, there are 2 CAR T-cell therapies approved to treat R/R MM with the goal of long-term disease control and improvement of patient quality of life, both of which received expanded approval to earlier lines of therapy in April 2024.

Idecabtagene vicleucel (ide-cel) is approved for the treatment of adult patients with R/R MM after 2 or more prior lines of therapy, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody. The phase III KarMMa-3 trial led to expanded approval from 4 or more to 2 or more prior lines of therapy.

Ciltacabtagene autoleucel (cilta-cel) is approved for the treatment of adult patients with R/R MM who have received 1 or more prior line of therapy, including a PI and an IMiD, and are refractory to lenalidomide. The phase III CARTITUDE-4 study of cilta-cel vs investigator’s choice standard of care led to expanded FDA approval from 4 or more to 1 or more prior lines of therapy.

Here I share my thoughts on key questions about managing patient expectations and concerns about CAR T-cell treatment, and best practices for posttreatment care.

What are the challenges with treating R/R MM and referring patients to treatment centers?
There are many treatment options available for patients with MM in the first to third relapse setting, so it can be difficult to determine which treatment is optimal for each patient when they relapse and when to consider CAR T-cell therapy. Selecting the optimal therapy should involve a discussion with your patients about tumor- and patient-specific factors, such as risk status and comorbidities.

If you work in the community setting, comanaging patients with an academic center can allow patients to receive most of their care locally and have the benefits of access to therapy from a larger center. I highly encourage advanced practice providers in community settings to talk with patients about referral to an academic center and not assume that a patient doesn’t want to be referred. Working with an academic center can help a patient’s care team determine the optimal treatment sequencing, including how to achieve the best results with CAR T-cell therapy. Ultimately, treatment decisions must be team decisions between the patient and the healthcare professionals, taking into consideration the risks and benefits and the financial and social support they have.

How do you manage patient expectations for the logistics of CAR T-cell therapy?
When you discuss the potential for CAR T-cell therapy for your patients with R/R MM, it is important to communicate expectations for CAR T-cell treatment logistics from the beginning to ensure patients understand the process and the need to follow guidelines by the letter for medical necessity. After harvesting T-cells, the manufacture of CAR T-cells can vary from 4 to 8 weeks, depending on the product, before lymphodepletion and reinfusion. Preparing and completing CAR T-cell treatment is a lengthy process and, although providers often say that CAR T-cell therapy is “one and done”, it's important that patients understand this therapy is followed by ongoing supportive care and monitoring.

For example, patients must refrain from driving for at least 8 weeks and remain within 2 hours of the hospital for at least 30 days after infusion. We also need to ensure patients have a dedicated caregiver for those 30 days and that the caregiver understands what that process will look like for them. Arranging this care can be challenging and it can be a difficult discussion with patients who don’t have someone to fill this role. We try to encourage them not to hire caregivers because we want somebody who is going to personally care about them, but we can also consider things like alternating care with rotating caregivers if one cannot be found for the entire 30 days. It is important that patients fully understand the commitment CAR T-cell therapy entails before beginning the process.

What are common patient concerns about beginning CAR T-cell therapy?
In addition to concerns about posttreatment logistics, patients who have undergone autologous stem cell transplant often fear going back to the hospital and worry that CAR T-cell therapy will be harder to handle. Their concerns about the risk of adverse events (AEs) are reasonable, so it’s important to discuss potential AEs with them as well as put the risk into perspective. I like to talk about these risks in categories of short-term toxicities and long-term toxicities. In the short term, we worry about cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and infection, but I reassure patients that we know how to manage these toxicities.

In the long term, we still see risk of infection as well as rare risk of delayed neurotoxicities, such as Guillain-Barré and Parkinsonian symptoms, which could be devastating to younger patients. We don’t have a good understanding of how or why this happens, but I emphasize that we're very closely monitoring their neurotoxicity scores and working with neurology colleagues at the same time.

In addition, the FDA has issued a black box warning on all CAR T-cell therapies for risk of secondary primary T-cell malignancies, which was first detected among patients with lymphoma after treatment. We do see an increased signal of secondary cancers in patients with MM that we don't quite understand, but I emphasize to patients that we are watching them closely with PET scans, whole body scans, and regular blood work and that CAR T-cell therapy is still very effective.

What is the most common secondary malignancy post CAR T-cell therapy?
Although the FDA black box warning is for T-cell malignancies, the most common secondary malignancies after CAR T-cell therapy are secondary leukemias, often myelodysplastic syndromes (MDS). My institution has a clonal hematopoiesis of indeterminate potential (CHIP) clinic that can test for specific changes to bone marrow to detect MDS and we are seeing high incidence of secondary MDS. Unfortunately, you need next-generation sequencing and very sophisticated techniques to detect these changes, so collaboration between community and academic centers becomes important. If patients aren’t being treated at a larger institution with these capabilities, we need to discuss what tests should be performed to monitor for those secondary malignancies.

What should the revaccination schedule look like after CAR T-cell treatment and what is the efficacy of revaccination?
This is a key question right now and, although we have some guidelines from the Center for International Blood and Marrow Transplant Research and the Infectious Diseases Society of America, clinical practice varies by institution. At my institution, we are beginning revaccination 6 months after treatment, and we usually have infectious disease practitioners working with our patients. If the patient is referred to us from a community center several hours away, we give them a chart that tells them when to receive their vaccines.

Regarding the efficacy of revaccination, there were several abstracts presented at the American Society of Hematology annual meeting in December 2024 on the subject. For instance, there are some data showing that administering 3 flu vaccines leads to higher blood antibody levels than 2 flu vaccines for patients with MM. Risk of infection is a big concern after CAR T-cell therapy, so we do recommend and encourage immunizations for our patients.

Your Thoughts
Have you talked to patients about the logistics of CAR T-cell therapy? Tell us about your experience in the discussion section below.