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

CD19 chimeric antigen receptor T cells (CD19-CAR) are effective at eradicating bone marrow (BM) B-cell acute lymphoblastic leukemia (B-ALL), but efficacy data for the treatment of extramedullary leukemia are lacking. We conducted a multisite, 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; n = 21), or isolated BM disease (iBM; n = 251) at infusion. The overall survival (OS) at 24 months in the iBM, EMD, and CNS cohorts was 71.5% (95% confidence interval [CI], 66.0-77.6), 66.7% (95% CI, 49.3-90.2), and 57.0% (95% CI, 42.6-76.3), respectively (P = .032); the 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 = .035). All patients with isolated EMD (n = 5) achieved complete response and did not relapse. Eight patients (80%) with isolated CNS disease (n = 10) had clearing of the CNS, and 3 (37.5%) subsequently relapsed. Concurrent EMD or CNS disease with high BM disease burden (HD) was associated with inferior outcomes when compared with low BM disease burden (LD) in terms of OS (EMD-HD, 41.7% vs EMD-LD, 100%; P = .005; CNS-HD, 33.3% vs CNS-LD, 92.3%; P = .001) and EFS (EMD-HD, 8.3% vs EMD-LD, 100%; P< .001; CNS-HD, 14.3% vs CNS-LD, 63.6%; P< .001). 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 preinfusion evaluation and treatment.