Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK) inhibitors. However, there is no standard treatment and limited published data evaluating their use. The goal of this retrospective study is to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL. We conducted a retrospective, multi-institutional study identifying 81 patients with R/R ALK-positive ALCL ≤ 21 years old at initial diagnosis treated between 2011-2022 across 18 institutions. Median time from diagnosis to relapse was 8.9 months (range 2.6-131.9). Initial reinduction regimens included ALK inhibitor monotherapy (n=37, 46%), BV monotherapy (n=19, 23%), chemotherapy without targeted therapy (n=12, 15%), chemotherapy with targeted therapy (n=9, 11%), or vinblastine monotherapy (n=4, 5%) with 83% of patients achieving a complete response to initial reinduction regimen. Fifty-eight patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 48 allogeneic, with one receiving both. Duration of treatment for patients receiving BV or the ALK-inhibitor crizotinib (CZ) varied widely (BV 1-11 years
CZ 2-10 years). Five-year event-free survival 63% (95% CI 53-75%) and five-year overall survival 91% (95% CI 84-98%). This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy and role of HSCT.