CD19 CAR T-cell outcomes in relapsed/refractory extramedullary B-ALL: a multi-site, retrospective cohort review

CD19 chimeric antigen receptor T-cells (CD19-CAR) are effective in eradicating bone marrow (BM) B-cell acute lymphoblastic leukemia (B-ALL), but efficacy data in treating extramedullary leukemia is lacking. We conducted a multi-site, retrospective review of 308 children and young adults who received CD19-CAR and report efficacy in patients with active central nervous system (CNS) disease (CNS cohort, n=36), active non-CNS extramedullary disease (EMD cohort, n=21), or isolated BM disease (iBM cohort, n=251) at infusion. Overall survival (OS) at 24-months in the iBM, EMD, and CNS cohorts was 71.5% (95%CI: 66.0-77.6%), 66.7% (95%CI: 49.3%-90.2%), and 57.0% (95%CI: 42.6-76.3%), respectively (p=0.032); corresponding event-free survival (EFS) was 51.8% (95%CI: 45.8-58.6%), 45.8% (95%CI: 28.2-74.4%), and 35.2% (95%CI: 22.4-55.3%) (p=0.035). All patients with isolated EMD (n=5) achieved CR and did not relapse. Eight (80%) patients with isolated CNS disease (n=10) cleared the CNS with 3 (37.5%) subsequently relapsing. Concurrent EMD or CNS disease with high disease burden (HD) was associated with inferior outcomes compared to low disease burden (LD) in terms of OS (EMD-HD 41.7% vs. EMD-LD 100%, p=0.005; CNS-HD 33.3% vs. CNS-LD 92.3%, p=0.001) and EFS (EMD-HD 8.3% vs. EMD-LD 100%, p<0.001; CNS-HD 14.3% vs. CNS-LD 63.6%, p<0.001). Outcomes for patients with HD and concurrent EMD or CNS disease were worse than for iBM patients with HD. In summary, CD19-CAR may be an effective option for relapsed/refractory B-ALL with active EMD or CNS disease, but concurrent HD predicts inferior outcomes, prompting consideration of enhanced pre-infusion evaluation and treatment.