A research study led by the University of Kansas suggests that the FDA-mandated monitoring period of diffuse large B-cell non-Hodgkin lymphoma patients receiving chimeric antigen receptor (CAR)-T cell therapy could be halved without harm to patients.
Writing in the journal Blood Advances, first author Nausheen Ahmed, a researcher and hematologist at the University of Kansas Medical Center, and colleagues report that side effects from the therapy such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) are very rare in patients with this type of lymphoma after two weeks.
CAR-T cell therapy has revolutionized treatment for high-grade blood cancers such as lymphoma and leukemia, but serious side effects like ICANS and CRS are relatively common. For this reason, the FDA put a strategy in place to reduce risk for patients that requires them to remain within two hours of the treatment center they are assigned to for four weeks after receiving their CAR T-cell therapy.
Many approved treatment centers insist on even stricter monitoring rules than this, for example, that patients must be within 30–60 min drive of the treatment center and have an assigned caregiver.
Although these restrictions are designed to keep patients as safe as possible, they are very restrictive as many people who need these therapies live more than 30 minutes away from an approved treatment center.
“As a clinician that administers CAR-T, I’ve had many patients who have not been able to receive it because of barriers to access,” said Ahmed in a press statement. “I have patients who are traveling for six or even eight hours to get treatment.”
For the current study, Ahmed and team assessed the timing and duration of CRS and ICANS, as well as other causes of death, in a cohort of 475 patients with diffuse large B-cell non-Hodgkin lymphoma being treated with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel)—all CD19-directed CAR-T cell therapies approved to treat this form of lymphoma.
Overall, the incidence of CRS was 60% and of ICANS was 32.4% in the group, with the majority of these reactions happening in the first week after the initial infusion of CAR-T cells.
The researchers noted some differences in the onset and duration of CRS and ICANS for each of the three therapies, but new cases of these adverse events were extremely unlikely two weeks after the treatment or later. No patients experienced new CRS after two weeks of monitoring and only one patient experienced new onset ICANS in the third week after their treatment.
Ahmed and colleagues believe the initial monitoring period could be safely reduced to two weeks. “We are learning that infection may be driving a lot of the non-relapse mortality and toxicity within the first few months after CAR-T infusion, so we have to shift our focus to preventing and managing infections after those two weeks,” noted Ahmed.
“Instead of the approved treatment center trying to keep the patient locally for a long time, we could collaborate with and train community hematologists/oncologists and referring physicians to identify, initiate treatment for, and collaborate with the approved treatment center to manage infections and other less common side effects.”
