Researchers Offer Road Map for CAR T-Cell Treatment for B-ALL

The researchers outlined patient selection for treatment, adverse event management, and future strategies for the treatment of these patients.

Offering a blueprint for children and young adults receiving chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoblastic leukemia (B-ALL), researchers are outlining patient selection for treatment, adverse event management, and future strategies for the treatment of these patients.

Their findings were published in Blood Reviews.

Patient Selection

Real-world data collected since the approval of tisagenlecleucel have supported its use in a broader patient population than its currently indicated for—patients younger than 26 years who are refractory or in second or greater relapse.

Since the pivotal phase 2 ELIANA trial, real-world registries have compiled data on patients, finding tisagenlecleucel is being used in a more diverse group of patients than were included in the trial.

Although patients included in these registries have had a similar median age and rate of allogeneic stem cell transplant (alloSCT) as those in the trial, in contrast to the ELIANA trial, the registries also include patients who are younger than 3 years, have extramedullary disease, and have active nervous system disease.

“These findings suggest both that a broader patient population than the one defined by trial eligibility criteria may benefit from tisagenlecleucel treatment and that increased experience treating patients with CAR T-cell therapy and treatment in the setting of lower disease burden may ultimately lead to continued improvement in overall patient outcomes,” wrote the researchers.

Managing Adverse Events

Cytokine release syndrome (CRS) and neurological toxicities are both commonly reported with CAR T-cell therapy. Grade ≥3 CRS has been reported in 14% to 49% of patients with a median onset of 3 to 5 days in 3 trials of CAR T-cell therapy in B-ALL.

In the pivotal ELIANA trial, CRS was managed with fluid bolus or vasopressors for hypotension, intubation, dialysis, tocilizumab, and corticosteroids. According to the researchers, some centers have started to use tocilizumab earlier in the management of CRS. A trial at Seattle Children’s Hospital indicted that early intervention with the immunosuppressive drug and systemic corticosteroids lowered the risk of severe CRS while preserving treatment efficacy.

Neurological toxicities that were grade 3 or higher have been reported in 8% to 13% of patients in trials, with a median onset of 7 days. Management of these toxicities include supportive care as frontline management (eg, prophylactic anticonvulsants). In the ELIANA trial, low-dose corticosteroids were strongly discouraged unless required for concurrent CRS. The researchers note that ongoing studies are assessing siltuximab and anakinra to treat neurotoxicity.

A Look Toward the Future

The researchers of the paper highlighted the short follow-up of patients with B-ALL receiving CAR T-cell therapy.

“Compared with alloSCT, after which patients may experience chronic [graft-versus-host disease] along with many other late effects, patients who received CAR T-cell therapy appear to avoid severe long-term side effects,” commented the researchers. “While the first child treated with tisagenlecleucel remains in remission 8 years later, data with longer-term follow-up are needed to understand the long-term efficacy of CAR T-cell therapy compared with transplant and whether and for which patients alloSCT may be necessary while in remission after CAR T-cell therapy.”

The researchers also highlight a need for new therapies for the patients who do not respond to CAR T-cell therapy and for those whose disease comes back. These options may include enrolling in a trial that tests the reinfusion of alternative CAR T-cell therapies or further treatment with immunotherapies, such as pembrolizumab.


Laetsch TW, Yanik GA, Boyer MW, Rheingold SR. An owner's manual for CD19 “CAR”-T cell therapy in managing pediatric and young adult B-cell acute lymphoblastic leukemia. Blood Rev. Published online May 6, 2021. doi:10.1016/j.blre.2021.100848