Outcomes of CD19 CAR T in Transformed Indolent Lymphoma Compared to De Novo Aggressive Large B‐Cell Lymphoma

ABSTRACT Chimeric antigen receptor (CAR) T‐cell therapy has revolutionized treatment of aggressive large B‐cell lymphoma (aLBCL). Patients with transformed indolent non‐Hodgkin lymphoma (tiNHL) were included in key CAR trials, but outcomes of CAR for this distinct, historically high‐risk group are poorly understood. We conducted a multicenter retrospective study of 1182 patients with aLBCL receiving standard‐of‐care CAR T between 2017 and 2022, including 338 (29%) with tiNHL. Rates of grade ≥ 3 cytokine release syndrome (CRS) were similar between tiNHL and de novo cohorts (7% vs. 8%, p = 0.6), while grade ≥ 3 immune effector cell‐associated neurotoxicity syndrome was lower in tiNHL (21% vs. 27%, p = 0.02). Overall response rate was similar in both cohorts (83% vs. 81%, p = 0.3), while complete response rate was higher in tiNHL (67% vs. 59%, p = 0.017). With a median follow‐up of 22.3 months, the progression/relapse‐free (PFS) and overall survival (OS) were similar between the tiNHL and de novo cohorts (24‐month PFS 41% [95% CI: 35%–46%] vs. 38% [95% CI: 35%–42%]; 24‐month OS 58% [95% CI: 52%–63%] vs. 52% [95% CI: 48%–56%], respectively). After adjusting for key risk factors, there was a trend toward a lower hazard of disease progression, relapse or death post‐CAR for tiNHL patients compared to de novo aLBCL patients (HR: 0.84 [95% CI: 0.69–1.0], p = 0.07). Elevated LDH, advanced stage, prior bendamustine within 12 months of CAR, receipt of bridging therapy, CNS involvement, and ≥ 3 prior lines of therapy were each associated with inferior PFS. In conclusion, CAR T therapy is highly effective with an acceptable toxicity profile in patients with tiNHL.