Outpatient CAR-T Cell Therapy May Be Safe in Hematologic Malignancies

Receiving CAR-T cell therapies in an outpatient setting may be safe and feasible without intensive remote monitoring with an early cytokine release syndrome (CRS) intervention strategy in patients with hematologic malignancies, according to data from a retrospective review. 

According to the National Cancer Institute, CRS is a condition that may occur after some types of immunotherapies like CAR-T cell therapy, and is caused by a rapid release of cytokines, which are immune substances with different actions in the body. Cytokines released in the blood may lead to signs and symptoms including nausea, fever, rash, headache, low blood pressure, rapid heartbeat and trouble breathing.

In this retrospective review, published in Blood Advances, 58 patients with hematologic malignancies who received CAR-T cell therapy in the outpatient setting during 2022 to 2023 were analyzed. Among patients in the study, 33 had myeloma, 24 had lymphoma and one had acute lymphoblastic leukemia.

Between zero to three days after CAR-T cell infusion, 17 patients (41%) were admitted to the hospital, followed by 16 patients (38%) admitted between days four and seven and nine patients (21%) admitted between days eight to 30.

“The use of remote monitoring systems/devices adds to health care resource utilization, can lead to patient anxiety and result in excessive reliance on these devices, thus delaying medical care,” study authors wrote. “We did not implement such remote monitoring systems and relied on patient and caregiver education, as well as on a system that has worked in our outpatient autologous and allogeneic transplant recipients for over a decade.”

Grade 1 (mild) to 2 (moderate) CRS occurred in 51 patients in the study, with no cases of grade 3 (severe) or worse CRS. The majority of patients who developed CRS (48 patients) received treatment with Actemra (tocilizumab).

Researchers also assessed the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS), which is a neurological side effect of CAR-T cell therapy during which the immune system attacks the nervous system and brain. Of the 20 patients who developed ICANS, 11 had severe grade 3 to 4 ICANS, all of whom required inpatient treatment. The most common reason for hospital admission was due to side effects related to CAR-T cell therapy, occurring in 33 out of 42 patients.

This data suggests a more tailored approach when treating patients with CRS and ICANS.

In 15 out of 35 patients who experienced CRS, hospitalization was prevented by administering the drug Actemra in an outpatient setting.

Of note, the percentage of patients who died without recurrence of their disease was 1.7% at one month and 3.4% at six months within the time frame. The cause of these deaths were related to refractory ICANS.

In this intervention, patients were seen daily (including weekends) in the cancer center day hospital for the first seven to 14 days after CAR-T cell therapy, and then twice weekly until day 30 in the general hematology outpatient clinic. After-hours patient check-ins via telephone or electronic devices were not used to track vital signs or patient symptoms during this time.

Early intervention for CRS involved administering Actemra in the outpatient setting for patients with grade 1 or worse CRS. Patients were admitted to the hospital if they developed higher than grade 1 CRS, ICANS, evidence of hemodynamic compromise, and neutropenic fevers.

This study also demonstrates that low-grade cytokine release syndrome may be managed in the outpatient setting using an early intervention strategy, thus preventing hospital admission and saving inpatient resources for others.

“We demonstrate that CAR-T cell therapy can be successfully administered as outpatient in a suitable setting, which includes patient and caregiver education regarding CAR-T cell– related toxicities, a 24-hour available center for monitoring patients in case of toxicity, and a well-trained nursing staff and physician (including on-call physicians),” study authors concluded.

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