Dr Mehta on Risks of CAR T-cell Therapy in Heavily Pretreated Lymphoma Patients

Amitkumar Mehta, MD, associate professor of medicine, associate director, Hematology and Oncology Fellowship Program, director, Phase I Program, co-director, CAR-T Program, University of Alabama at Birmingham (UAB) Bone Marrow Transplant Program, co-director, Cutaneous T Cell Lymphoma Clinic, The Kirkin Clinic, director and principal investigator, Lymphoma Tissue Bank, director, UAB Lymphoma Working Group, UAB Medicine, discusses the risks associated with CAR T-cell therapy in patients with lymphoma who have undergone multiple lines of prior chemotherapy.

Patients receiving CAR T-cell therapy later in their treatment course often face an elevated risk of secondary malignancies due exposure to prior lines of cytotoxic chemotherapy, Mehta explains. This can predispose patients to myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Additionally, there is emerging evidence suggesting that CAR T-cell therapy itself may contribute to the development of secondary T-cell lymphomas, he continues. Mehta notes that cases like this have demonstrated a potential clonal relationship between the CAR-modified T-cells and the newly developed lymphomas, though further research is required to confirm this risk.

Infections are another significant concern for patients undergoing CAR T-cell therapy, he states. Many of these patients have received rituximab (Rituxan) and other chemotherapy agents, which can result in hypogammaglobulinemia and increase the risk of infections, including severe viral infections like COVID-19. For example, infections occurred in approximately 75% of patients receiving the treatment, with 35% experiencing grade 3/4 infections which required interventions such as intravenous antibiotics or hospitalization. Notably, infection rates were higher during the first 3 months of treatment but declined over time.

Mehta emphasizes that cytopenia’s, particularly neutropenia, are well-defined risks following CAR T-cell therapy, further heightening the risk for bacterial infections. Given the complexity of these risks, it is essential to discuss the benefits and potential complications of CAR T-cell therapy with patients.

Ongoing research will help clarify the long-term risks, particularly the potential for secondary malignancies in this heavily pretreated patient population, Mehta concludes.