CD19 CAR T‐Cell Therapy for Primary Mediastinal Large B‐Cell Lymphoma: A CIBMTR Analysis

ABSTRACT T cells engineered with CD19‐directed chimeric antigen receptors (CD19 CAR) T cells have become standard treatment for patients with high risk, relapsed or refractory (R/R) large B‐cell lymphomas (LBCL). However, outcomes in patients with rare subsets of LBCL, such as primary mediastinal large B‐cell lymphoma (PBMCL), have not been well characterized. The impact of prior immune checkpoint inhibitor (ICI) treatment, commonly used to treat R/R PMBCL, is also unknown. To address these gaps, we retrospectively analyzed CIBMTR registry data including PMBCL patients undergoing CD19 CAR T‐cell therapy per standard‐of‐care. A total of 135 PMBCL adults from 66 centers were included. Median age at the time of CAR T‐cell therapy was 32. Thirty‐nine patients (28.9%) had received an ICI prior to CAR T‐cell therapy. The best overall and complete response (CR) rates after CD19 CAR T‐cell therapy were 79% and 67.7%, respectively. The 2‐year progression‐free (PFS) and overall survival (OS) were 58.6% (95% CI, 49.7–67.3) and 80.8% (95% CI, 72.6–87.8), respectively. The 2‐year cumulative incidence (CI) of relapse and non‐relapse mortality (NRM) were 36% (95% CI, 27.8–44.7) and 5.4% (95% CI, 1.9–10.5), respectively. We observed grade ≥ 3 CRS and ICANS in 6.1% and 14.7%, respectively. Prior ICI exposure was associated with lower 2‐year CI of relapse (ICI‐exposed, 21.7%; ICI‐naïve, 41.6%; p = 0.03) and higher 2‐year NRM (ICI‐exposed, 11.7%; ICI‐naïve, 2.8%; p = 0.03). We could not confirm statistically different PFS ( p = 0.19) or OS ( p = 0.26) between ICI‐exposed and ICI‐naïve patients. CD19 CAR T‐cell therapy led to high rates of durable responses in PMBCL patients with low rates of severe toxicities.