International Patients Paths to Chimeric Antigen Receptor T-Cell Therapy for B-ALL: No Two Journeys Are Alike

PURPOSE Chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) has a critical role in improving outcomes. Access to CAR T-cell therapy is limited for international patients for whom standard therapies have failed, forcing many to undertake substantial travel in search of a cure. Our institution offers phase I CAR T-cell clinical trials for pediatric, and adolescent and young adult (AYA) patients, and is one of few that can accept patients nationally and internationally. METHODS This was a retrospective study of international patients with r/r B-ALL enrolled on a CAR T-cell trial at the pediatric oncology branch (POB) from 6/2012 through 3/2021. Variables including demographics and prior therapies (among others) were manually extracted from the electronic medical records, and analyzed using Microsoft Excel and R software, version 4.3. RESULTS A total of 57 patients (71.9% male) were included, including 35 (61.4%) from high income countries (World Bank Classification), 14 (24.6%) from upper-middle income countries, and 8 (14.0%) from low-middle income countries. Most common referrals were for a relapse after hematopoietic stem cell transplantation (HSCT) and/or CAR T-cell (43.9%), followed by CD19 negative relapse/refractory disease (29.8%). Twenty-six patients (45.6%) were enrolled for CD22, 21 (36.8%) for CD19, and 10 (17.6%) for dual CD19/CD22 directed CAR T-cell therapy. The median number of prior therapy lines was 5 (range 2-12, Q1 = 4, Q2 = 6). Thirty-five patients (61.4%) underwent at least one prior HSCT, 29 (50.1%) had received prior immunotherapy, and 19 patients (33.3%) received at least one prior CAR T-cell at other institutions “Only 3 of 21 CAR T-cell products (14.3%) were received in the patient's home country. Twenty-six patients (45.6%) received chemotherapy to control the disease during travel to our institution for enrollment, 47 patients (82.5%) received at least one anti-microbial prophylactic agent, and 26 patients (49.1%) had central venous access on arrival. Median age at CAR T-cell infusion was 13 years (Q1 = 9, Q3 = 20). CONCLUSION Our study is the largest to describe prior lines of therapy and treatment paths for international pediatric and AYA patients with relapsed/refractory B-ALL undergoing CAR T-cell therapy. Characterizing prior therapies and paths of this heavily treated population will help inform future directions in expanding this novel immunotherapy availability and addressing access disparities across the world.