Maintenance therapy for early loss of B-cell aplasia after anti-CD19 CAR T-cell therapy

Chimeric antigen receptor (CAR) T -cell therapy has transformed the landscape of relapsed/refractory B -cell acute lymphoblastic leukemia (ALL) in children and young adults, (1,2) with a 3 -year relapse -free survival of 52% for tisagenlecleucel in the pivotal ELIANA trial. 3 B -cell aplasia (BCA) is an indirect measure of anti-CD19 CAR T -cell presence. Early ( <= 6 months from infusion) loss of BCA (LBCA) was associated with high relapse risk in studies with tisagenlecleucel or other 41BBz anti-CD19 CAR T -cell products. (4-9) However, with different anti-CD19 CAR T cells (eg, CD28-containing brexucabtagene), the long-term persistence of CAR T cells seems not required for durable remission. (10) The optimal therapeutic strategy for patients with early LBCA after tisagenlecleucel is unclear; good outcomes have been achieved with consolidative hematopoietic stem cell transplant (SCT). (3,9) However, SCT is associated with signi fi cant mortality, especially for patients with prior SCT within 12 months,( 11) and with long-term side effects. (12) Indeed, a benefit of consolidative SCT after CAR T -cell therapy has not been demonstrated for patients who have received prior transplant. (13) Moreover, not all patients have a suitable donor, and some are precluded from SCT because of comorbidities. At our center, children who received tisagenlecleucel and presented with early LBCA with a contraindication to SCT were treated with a maintenance chemotherapy regimen for 2 years, with promising early outcomes. (14 )Here, we report on the longer follow-up of a larger cohort of children and young adults from across the United Kingdom receiving maintenance chemotherapy or SCT after early LBCA. We retrospectively collected data of patients treated either with tisagenlecleucel or experimental 41BBz anti-CD19 and anti-CD19/anti-CD22 CART cells (NCT02443831) in the United Kingdom from June 2017 to June 2022. The data cut-off date was 20 March 2023. Data were collected on a health service evaluation basis, on the basis of outcome assessment after CAR T -cell therapy. Consent for data collection was obtained from patients, parents, or legal guardians. Inclusion criteria were early LBCA ( <= 6 months from infusion) without evidence of disease, de fi ned as morphological complete remission (CR) and negative measurable residual disease (MRD) by polymerase chain reaction analysis.