Second primary malignancy in patients with diffuse large B-cell lymphoma (DLBCL) receiving chimeric antigen receptor T-cell (CAR T) therapy and other systemic anti-cancer therapy: A real-world data analysis.

7080 Background: CAR T therapy is a recent class of treatment for DLBCL and has been linked to the development of second primary malignancy (SPM), specifically T-cell malignancies. This study compared the risk of SPM in patients (pts) with DLBCL receiving CAR T therapy vs other systemic anti-cancer therapy (SACT). Methods: Adult pts with a diagnosis of DLBCL who received CAR T therapy or other SACT as second or higher line of therapy (LoT) were identified from Komodo Health claims data (10/18/2017–1/31/2024). Incident SPM (first diagnosis in pts with no history of that malignancy) was assessed from index treatment initiation through earliest report of death, disenrollment from medical coverage, or data cutoff (4/30/2024). Cumulative incidence of SPM was calculated using the Aalen–Johansen estimator with baseline risk factors, including previous treatments and number of prior LoTs (pts may contribute to multiple LoTs), demographic and lifestyle factors, and comorbidity history balanced between the treatment groups using inverse probability of treatment weighting. Results: The study assessed a total of 1079 (CAR T therapy) and 5836 (SACT) LoTs over a median follow-up of 10.6 months (IQR 4.3–24.3). The risk of SPM (95% CI) at 3 years post-index tended to be nominally lower in the CAR T therapy group vs the SACT group for any (37.2% [33.4, 40.7] vs 41.6% [35.5, 48.7]), hematologic (27.4% [23.8, 30.7] vs 28.5% [22.8, 35.0]; excluding DLBCL relapse), solid (14.7% [12.3, 17.1] vs 18.4% [14.8, 23.0]) (Table) and T-cell (2.6% [1.7, 3.8] vs 4.3% [2.8, 5.9]) SPM. A sensitivity analysis identifying SPM using ≥2 ICD-10 codes showed similar associations. In another sensitivity analysis excluding SPMs occurring in the first 3 months of follow-up, the risk in the CAR T therapy group remained nominally lower for any, solid, and T-cell SPMs, and higher for hematologic SPM, compared with the SACT group (Table). Conclusions: A large proportion of pts with DLBCL experienced SPMs with current treatment options. At 3 years post-index, there was no evidence of an increased risk of SPM in pts treated with CAR T therapy compared with those receiving SACT. Longer term studies are needed to confirm this observation. Cumulative incidence (%) and 95% CI of SPM at 3 years post-index. SPM Analysis SACT CAR T therapy p-value Any Main 41.6 (35.5, 48.7) 37.2 (33.4, 40.7) 0.20 S1 32.4 (26.0, 40.3) 23.1 (20.0, 26.3) 0.08 S2 34.4 (27.7, 41.2) 32.5 (28.6, 36.2) 0.81 Hematologic Main 28.5 (22.8, 35.0) 27.4 (23.8, 30.7) 0.28 S1 20.1 (14.4, 26.2) 16.9 (14.2, 20.3) 0.35 S2 20.7 (15.3, 26.8) 22.9 (19.3, 25.9) 0.55 Solid Main 18.4 (14.8, 23.0) 14.7 (12.3, 17.1) 0.34 S1 13.8 (9.6, 18.6) 8.3 (6.4, 10.2) 0.11 S2 17.7 (12.8, 23.5) 13.6 (11.5, 16.2) 0.41 S1: ≥2 ICD-10 codes for SPM identification; S2: excludes SPM diagnosed in the first 3 months. S1/2, sensitivity analysis 1/2.