CAR T-Cell Therapy: Long-Term Side Effects and Patient Outcomes from ASH 2024

At the 66th American Society of Hematology (ASH) Annual Meeting, CAR-T therapy took center stage, showcasing its groundbreaking impact on treating relapsed and refractory blood cancers. This cutting-edge treatment has notably enhanced patients' chances of survival, making it a crucial option in the ongoing fight against these challenging diseases.

While much focus has been on CAR-T side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), the growing number of people experiencing lasting benefits highlights the importance of addressing long-term complications.

This article highlights key aspects of CAR T-cell therapy mentioned at ASH 2024, including late side effects, patient-reported outcomes, infection management, and best practices for its application.

Acute and Long-Term Side Effects of CAR T-Cell Therapy

CAR T-cell therapy has resulted in many patients with long-term disease-free outcomes from blood cancer, although it also comes with common side effects. For this topic, Dr. Michael Bishop addressed the known side effects of CAR T-cell therapy. 

• Acute side effects can be immediate or close to the date of infusion; they include ICANS and CRS; they can be sometimes mild but sometimes serious, and that's why in the first weeks after therapy, there is closer monitoring, and the treatment should be immediate.
• Long-term side effects can appear more than 90 days after infusion; the most common is low blood cell counts. People can be at higher risk of infections, secondary malignancies (cancer), including rare T-cell cancers, and cognitive and functional impairments.

We had the privilege of interviewing Dr. Michael Bishop from the David and Etta Jonas Center for Cellular Therapy at the University of Chicago. In the video below, Dr. Bishop discusses the late complications and long-term care considerations for patients who have received CAR T-cell therapies. Key points include:

• The vulnerability of the immune system after CAR T therapy leading to a higher risk of infections
• How CAR T cell therapy can affect blood cell counts
• The evaluation of how the benefits of CAR T therapy outweigh the risks of developing secondary malignancies, a topic that has received significant attention over the past year, particularly in the treatment of lymphoma

Mitigating and Managing Infection Risk in Adults Treated with CAR T-cell Therapy

Dr. Nadeem Tabbara, from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, reviewed the best strategies to reduce the infections that we now understand can be more frequent in patients who received CAR T-cell therapy. Here are some recommendations mentioned during the session: 

• Regular monitoring of blood counts and bone marrow function to detect cytopenias or signs of secondary malignancy
• Preventive measures against infections
• Implementation of re-vaccination programs to restore immunity
• Growth factors to promote blood-producing cells' recovery

Immune recovery can be slow due to the targeting of normal B cells and plasma cells, which are in charge of protecting the body against infections. This means patients could experience long periods of low white blood cell counts in their blood analysis and a higher risk of infections. These often require prophylaxis and immunoglobulin replacement therapy (IVIG). Vaccinations are recommended but may have reduced efficacy.

A multidisciplinary approach between oncologists and cell therapy centers is critical for monitoring and managing these late complications, improving long-term outcomes and quality of life for CAR T-cell therapy recipients.

Patient-Reported Outcomes: A Vital Component to Improve Care

Patient-reported outcomes (PROs) are revolutionizing how doctors understand and improve CAR T-cell therapy experiences. These valuable insights, gathered directly from patients, help healthcare teams deliver more personalized and effective care. This presentation highlighted the current use of PROs, practical solutions, and future directions to make PROs a key part of CAR T-cell therapy, empowering patients to have a stronger voice in their care.

Key Benefits of Patient-Reported Outcomes in CAR T-Cell Therapy:

• Real-time symptom monitoring and faster medical response
• More personalized treatment approaches
• Better communication between patients and healthcare teams
• Improved understanding of long-term effects
• Enhanced quality of life management

Mental Health Insights from CAR T-Cell Therapy Patients

Recent research reveals important mental health patterns among CAR T-cell therapy survivors. This is one of multiple examples of the type of information that PROs can provide. According to a study by Ruark and colleagues:

• 47% of patients experienced cognitive challenges, depression, or anxiety
• 17.5% reported significantly lower mental health scores
• 37% noticed cognitive changes after treatment
• Possible links emerged between acute neurotoxicity and cognitive effect

These findings highlight why mental health screening and support should be essential components of long-term CAR T-cell therapy care.

Final Thoughts

In conclusion, the 66th ASH Annual Meeting highlighted the impact of CAR T-cell therapy in treating relapsed and refractory myeloma and lymphoma while emphasizing the importance of addressing both acute and long-term complications.

Managing side effects such as low blood cell counts, infections, and secondary malignancies is critical to ensuring sustained benefits for long-term survivors. Moreover, incorporating patient-reported outcomes (PROs) into care protocols empowers patients and enhances treatment personalization, paving the way for improved quality of life and long-term success.

As research continues to evolve, collaboration between patients, oncologists, and therapy centers is vital to advancing CAR T-cell therapy and optimizing its application. 

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Sources: 

• Adult CAR-T Outcomes: Beyond the Acronyms (OS, PFS, CRS, ICANS)
• Patient-reported outcomes after CAR T-cell therapy in patients with hematological malignancies
• Late complications and long-term care of adult CAR T-cell patients
• Mitigating and managing infection risk in adults treated with CAR T-cell therapy