Epidemiological Features and Clinical Outcomes Predicting Risk and Prognosis of Transformed Marginal Zone Lymphoma: A SEER-Based Population Study

Aim: Diffuse large B-cell lymphoma (DLBCL) transformed from marginal zone lymphoma (MZL) is a rare subtype of non-Hodgkin's lymphoma. The clinical outcomes and prognosis of transformed MZL (trMZL) have not been well defined so for. Our study aimed to explore the epidemiology, clinical characteristics and survivals of trMZL with population-based data.

Method: A total of 315 cases of trMZL patients diagnosed from 2000 to 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression was utilized to estimate the risk factors of DLBCL transformation of MZL. Multiple linear regression was conducted to explore the risk factors of early DLBCL transformation in trMZL patients. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to investigate the epidemiological and clinical factors associated with the overall survival of trMZL patients from diagnosis (OS1) and from transformation (OS2), respectively. Cox proportional hazard regression was further used to determine the independent prognostic factors for OS1 and OS2. Nomograms were developed to predict survival possibilities of 5-, 10- and 15-years OS1.

Results: Overall incidence of DLBCL transformation in MZL was 1.58% (315/19675). The 2-, 5-, and 10-years cumulative incidence of DLBCL transformation was 0.41%, 1.13%, and 2.00%, respectively. The median age at diagnosis and at transformation of trMZL patients was 64 years old (range: 25 ~ 89) and 69 years old (range: 34 ~ 91), respectively, with female and White race predominance. Median OS1 and OS2 were 140.0 months (95% CI: 120.5 ~ 159.5) and 53.0 months (95% CI: 35.1 ~ 71.0) respectively, which were significantly worse than that of de novo MZL (median OS 195.0 months [95% CI: 187.77~ 202.3]) and de novo DLBCL (median OS 119.0 months [95% CI: 116.5 ~ 121.5]). Splenic marginal zone lymphoma and Ann Arbor stage III/IV were the risk factors for DLBCL transformation, whereas trMZL patients with older age at diagnosis, non-White race and without radiotherapy may be subjected to early transformation. Multivariate Cox regression demonstrated that five variables were significant prognostic factors associated with superior OS1 (P<0.05), including younger age at diagnosis, female, radiotherapy, surgery, and later DLBCL transformation. With regards to treatment modality, surgery plus radiotherapy could significantly improve patients' OS1 in comparison to chemotherapy-containing treatment regimes. However, only younger age at transformation and female were significantly associated with better OS2 (P<0.05). The nomogram for trMZL was established to predict 5-, 10-, and 15-years OS1 possibility, which was verified by a high concordance index [0.75 (0.73-0.77), P<0.05] and good agreement with the predicted value in calibration plots.

Conclusion: The trMCL is a rare neoplasm with a low incidence of DLBCL transformation. Splenic marginal zone lymphoma and advanced stage may increase the risk of DLBCL transformation in MZL patients. Patients with trMCL exhibited distinct clinical features and outcomes. In addition to younger age of onset, use of surgery plus radiotherapy and late DLBCL transformation were associated with favorable prognoses for trMZL patients.

No relevant conflicts of interest to declare.