Sept. 27, 2024
Chimeric antigen receptor-T cell therapy, or CAR-T cell therapy, is an innovative way to manage aggressive hematologic malignancies. But what is its role in patients with cardiac involvement of their lymphoma or underlying heart disease such as a reduced heart function? That's what Mayo Clinic cardio-oncologists and hematologists set out to answer. They presented their findings in a case report series published by the Journal of the American College of Cardiology (JACC) family of journals.
CAR-T cell therapy involves the infusion of genetically engineered autologous T cells. In recent years it's shown to be an effective treatment for selected patients with relapsed or refractory B-cell lymphomas.
"CAR-T cells are engineered immune cells that recognize a tumor cell target and destroy it. It's a sophisticated weapon in the war against cancer. The concern is what could go wrong from a cardiovascular perspective?" says Joerg Herrmann, M.D., a cardiologist at Mayo Clinic in Rochester, Minnesota, founder and director of the Cardio-Oncology Clinic at Mayo Clinic, and senior author of the case report. "Especially in cases where patients already have a reduced heart function, or involvement of the heart by the tumor, is it safe to do CAR-T cell therapy? This series of cases addressed that question."
The concern for using CAR-T cell therapy in these challenging cases is due to potentially life-threatening complications including:
- Ventricular rupture.
- Cardiac tamponade.
- Circulatory failure.
Case series findings
The case series included male and female patients ages 30 to 70 with lymphoma and cardiomyopathy or cardiac metastasis. Additional chemotherapy was given to patients to reduce the burden of cardiac involvement before CAR-T cell therapy.
"We felt the benefit of proceeding with CAR-T cell therapy outweighed the risk in these patients. Without therapy these patients would have died, and we treated them successfully," says Dr. Herrmann. "They had a good tumor response, and they didn't have any decompensation from a cardiovascular perspective."
The most common complications seen with CAR-T cell therapy after cytokine release syndrome (CRS) are cardiotoxicity and neurotoxicity. They can develop in the same patient simultaneously. About 57% to 93% of patients receiving CAR-T cell therapy experience CRS, presenting as fever, hypotension, hypoxia or multiorgan toxicity.
Treating patients with CAR-T cell therapy is a joint decision. The multidisciplinary approach is important and discussions often involve cardio-oncologists, hematologists and the patient.
Moving boundaries
Patients with preexisting cardiomyopathy, defined as an LVEF < 50%, and those with cardiac lymphomatous involvement can be managed safely and undergo CAR-T cell therapy without significant cardiac adverse events.
"This case series illustrates that the boundaries of cancer therapies can be moved, making treatments available to patients with malignancies who were historically excluded from CAR-T cell therapy in clinical trials," says Dr. Herrmann. "Reconsidering the limitations is important especially if no treatment alternatives exist. However, any consideration for therapy needs to be done carefully and with full understanding that complications may occur. As much as possible, the risk should be calculated, mitigated and prevented. This requires collaboration across disciplines and in these cases, close involvement of cardiologists."
Looking ahead
There is a need to hear if other centers had the same experience, what problems they encountered and how they overcame them, according to Dr. Herrmann. "It's important to share case series like these so knowledge about treatment options, their advancements and outcomes, are made available to patients and providers. Sharing our experiences is essential at Mayo Clinic and it has been from the beginning."
For more information
Ng CT, et al. CAR-T therapy in lymphoma patients with coexisting cardiomyopathy or cardiac lymphomatous involvement. JACC: Case Reports. 2023;15:101840.
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