(SLB-025) Second Primary Malignancy in Patients with Diffuse Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy and Other Systemic Anti-Cancer Therapy: A Real-World Evidence from a Large US National Claims Database

Background: Chimeric antigen receptor (CAR) T-cell therapy is a recent class of treatment for diffuse large b-cell lymphoma (DLBCL) and has been linked to the development of second primary malignancy (SPM), specifically T-cell malignancies. However, evidence from real-world studies is limited, warranting further investigation.

Objectives: The study aims to compare the risk of SPM between patients (pts) with DLBCL receiving CAR T-cell therapy and pts receiving other systemic anti-cancer therapy (SACT).

Methods: Adult pts with a diagnosis of DLBCL who received CAR T or other SACT in 2nd or higher lines of therapy (LoT) were identified from Komodo Health claims data between 10/18/2017 and 1/31/2024. Incident SPMs, defined as the first diagnosis among those with no prior history of that malignancy, were assessed from index treatment initiation through the earliest occurrence of death, disenrollment from medical coverage, or data cutoff (4/30/2024). The cumulative incidence of SPM and 95% confidence intervals were estimated using the Aalen-Johansen estimator with death as a competing risk. Baseline risk factors, including previous treatments and number of prior LoTs (pts may contribute to multiple LoTs), demographic and lifestyle factors, and comorbidity history were balanced between the treatment groups using inverse probability of treatment weighting to estimate the average treatment effect in the treated.

Results: A total of 1,079 (CAR T) and 4,583 (SACT) LoTs were included, with a median follow-up period of 10.6 mos. (interquartile range: 4.3 to 24.3 mos.). The risk of any SPM tended to be nominally lower in the CAR T group compared to the SACT group at 12 (23.3% [20.3, 26.3] vs. 27.3 [24.5, 30.2], 24 (32.3% [28.5, 36.3] vs. 34.8% [31.5, 38.4]) and 36 (37.2% [32.9, 41.6] vs. 38.5% [35.0, 42.4]) mos. (p=0.06 over 36 mos. of follow-up). Nominally lower risk was seen for solid SPM and was significantly lower for T-cell SPM (2.6% [1.4, 3.9] vs. 4.9% [3.6, 6.6]; p=0.01). The risk was similar for hematologic SPM at 36 mos. but higher for myelodysplastic syndrome (MDS) in the CAR T group (7.1% [4.8, 9.4] vs. 4.8% [2.8, 7.2]; p=0.05). A sensitivity analysis identifying SPMs using ≥2 ICD-10 codes showed similar associations. In another sensitivity analysis excluding SPMs occurring in the first 3 mos. of follow-up, the risk in the CAR T group remained nominally lower for T-cell SPM, higher for MDS, and was similar for any, solid and hematologic SPM, compared with the SACT group at 36 mos.

Conclusions: A large proportion of pts with DLBCL experienced SPMs. Through 36 mos. post-index, there was no evidence of an increased risk for SPM in pts with DLBCL exposed to CAR T treatment compared to SACT. Longer term studies are needed to confirm this observation.