Patients who received an early or prophylactic hematopoietic stem cell boost “showed quick response and improved outcomes” for sustained moderate to severe neutropenia occurring after chimeric antigen receptor (CAR) T-cell therapy, according to a recent study.
Nico Gagelmann, MD, of the University Medical Center Hamburg-Eppendorf in Germany, and colleagues conducted the study because hematotoxicity after CAR T-cell therapy is “associated with infection and death, but management remains unclear.”
The study included 31 patients, 20 of whom received axicabtagene ciloleucel, seven of whom received tisagenlecleucel, and three of whom received allogeneic CAR T cells. Most patients (81%) received CAR-T to treat diffuse large B-cell lymphoma. The median patient age at the time of CAR-T infusion was 62 years.
Of the 31 patients, 30 received an autologous hematopoietic stem cell boost and one received an allogeneic hematopoietic stem cell boost. The patients received a hematopoietic stem cell boost for either sustained severe neutropenia of grade 4, sustained moderate neutropenia and high risk of infection, or a neutrophil count ≤2.0 × 109/L and active infection.
The median duration of neutropenia before hematopoietic stem cell boost was 38 days, with a median absolute neutrophil count of 0.2 at the time of hematopoietic stem cell boost. The median time from CAR-T to hematopoietic stem cell boost was 43 days.
The overall neutrophil response rate, defined as recovery or improvement, was 84% within a median of nine days. The time to response was significantly associated with the duration of prior neutropenia (P=.007).
The one-year overall survival (OS) rate was 59%, but all patients who did not respond died within the first year after receiving a hematopoietic stem cell boost. The one-year OS rate was 85% in those with neutropenia for ≤38 days before hematopoietic stem cell boost, significantly higher than in those who had neutropenia >38 days before (44%; P=.029).
The study, which was the first to demonstrate that cryopreserved autologous hematopoietic stem cell boosts “generally result in prompt resolution of neutropenia, especially when given early after CAR-T,” may inform future treatment and research approaches, Dr. Gagelmann and colleagues wrote.
For example, prophylactic collection of autologous stem cells “may be considered for patients that are both fit and unfit for second-line autograft,” the study’s authors wrote, noting that “some of our centers have already started prophylactic collection even for patients who did not receive prior collection for an autologous transplant.”
Overall, Dr. Gagelmann and colleagues concluded early or prophylactic hematopoietic stem cell boost “showed quick response and improved outcomes for sustained moderate to severe neutropenia after CAR-T.”
Gagelmann N, Wulf GG, Duell J, et al. Hematopoietic stem cell boost for persistent neutropenia after CAR T-cell therapy: a GLA/DRST study. Blood Adv. 2023;7(4):555-559. doi:10.1182/bloodadvances.2022008042