Secondary primary malignancies (SPMs) with CAR-T cell therapy in RR-DLBCL from real-world data.

7066 Background: Three CAR-T cell therapies i.e. axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel are currently approved for relapsed refractory DLBCL after 2 or more prior lines of treatment. Landmark trials have shown promising efficacy however, a notable concern with CAR-T therapy is the potential development of secondary primary malignancies. Methods: A retrospective study was performed using TriNetX, a global research de-identified database with data from 145 health care organisations as of January 2025. ICD-10 codes were used for associated diagnosis and medications. The database was queried to identify RR-DLBCL patients who had received any of axi-cel, tisa-cel or liso-cel. These treatments were set as the index event for outcome analysis. Demographics and prevalence of comorbidities were extracted. Outcome analysis queried for several hematological and solid tumor malignancies. The Measure of Association Analysis was used to calculate Odds Ratio. Results: 1842 adult patients with RR-DLBCL received one of the 3 CAR-T cell treatments as listed above and 12,431 patients with RR-DLBCL did not receive any of the 3 treatments. There were 1:1 propensity score matched adjusting for age, race, sex and tobacco use. Final number for both groups was 1842. For both cohorts, 1367 (73.8%) were white, 1055 were male (57%). The cohort had a mean follow up of 497 days, median follow up of 331.5 days. The CAR-T group had higher rates of MDS (3.9% vs 0.8%, p=<0.001) and AML (3.2% vs 1.2%, p=<0.001) in our database review of the US population. It did not show higher rates of other reported SPMs like Mature T/NK cell lymphoma, Hodgkin's lymphoma, multiple myeloma or solid tumours like lung, breast, prostate primary or malignant melanoma. Data on other SPMs is shown in Table 1. Conclusions: In our retrospective study of real-world population, RR-DLBCL patients who received CAR-T cell therapy with any of axi-cel, tisa-cel or liso-cel showed higher rates of MDS and AML compared to propensity matched patients with RR-DLBCL who did not receive CAR-T cell therapy while rates of other reported SPMs were not significantly different. Frequency of SPMs in CAR-T receiving and no CAR-T receiving patients with RR-DLBCL. SPM Received CAR-T cohort (%) Did not receive CAR-T cohort (%) Odds Ratio p-value MDS 3.9 0.8 4.852 (2.767-8.507) <0.001 AML 3.2 1.2 2.668 (1.624-4.382) <0.001 Mature T/NK cell lymphoma 0.7 1.5 0.466 (0.238-0.909) 0.022 Hodgkin's lymphoma 0.9 1.9 0.469 (0.257-0.854) 0.011 Follicular lymphoma 3.8 3.6 1.055 (0.721-1.545) 0.781 Mantle cell lymphoma 1.0 0.5 1.792 (0.825-3.893) 0.135 Multiple Myeloma 1.4 2.4 0.566 (0.341-0.938) 0.025 Primary Lung site 0.7 0.5 1.292 (0.565-2.954) 0.543 Primary Breast site 0.5 0.7 0.815 (0.351-1.892) 0.634 Prostate cancer 0.5 0.6 0.902 (0.382-2.129) 0.814