Incidence of Second Primary Malignancies in Mantle Cell Lymphoma: US Population-Based Study from 2000- 2021
Authors: Bhanushali Charmi , Mukhtiar Vaibhavi P , Kasire Sripada Preetham , Jayakumar Jayalekshmi , Rajarajan Srinishant , Babu Kalaivani , Roy Arya Mariam 
Published: December 2024

Introduction:
Mantle cell lymphoma (MCL) is a rare aggressive subtype of Non-Hodgkin lymphoma (NHL) whose prognosis has notably improved in recent years. Patients with MCL are at an elevated risk for developing second primary malignancies (SPMs). Given the advancements in treatment and survival outcomes, this study aims to analyze the incidence of SPMs among MCL patients within a U.S. population-based framework from 2000 to 2021.
Methodology:
We utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (version 8.4.3) to identify patients with a histological diagnosis of MCL (ICD-O-3 code 9673/3) between 2000 and 2021. To determine the sites of second primary cancers, we used the SEER site recode based on ICD-O-3 site and histology classifications. Using multiple primary standardized incidence ratio (MP-SIR), we calculated SIR of SPM and stratified the results based on age, sex and race.
Results:
Our findings indicate that patients with MCL have a 41% heightened risk of developing SPMs (95% confidence interval (CI) 1.34-1.49, p &lt; 0.05) compared to the general population. Within specific demographic subgroups, the SIR was statistically significant for Caucasians (1.42, p &lt; 0.05) and Asian or Pacific Islander populations (1.64, p &lt; 0.05). The mean interval from MCL diagnosis to the onset of an SPM was 58 months. Notably increased risk was identified for various solid tumors, including salivary glands (SIR 2.53; CI 1.01-5.2, p &lt; 0.05), respiratory (SIR 1.53; CI 1.32-1.76, p &lt; 0.05), skin [excluding basal and squamous cell carcinomas] (SIR 2.16; CI 1.8-2.58, p &lt; 0.05), melanoma (SIR 1.87; CI 1.52-2.28, p &lt; 0.05), renal (SIR 1.69; CI 1.2-2.21, p &lt; 0.05), and thyroid cancers (SIR 3.68; CI 2.59-5.07, p &lt; 0.05). Hematological malignancies had higher SIRs reported for NHL (2.23; CI 1.79-2.74, p &lt; 0.05), chronic lymphocytic leukemia (2.72; CI 1.89- 3.78, p &lt; 0.05), acute lymphocytic leukemia (4.88; CI 1.31- 12.5, p &lt; 0.05) and myeloid and monocytic leukemia (5.55; CI 4.32- 7.01, p &lt; 0.05). The risks for thyroid, renal, and respiratory cancers were elevated in the first year following MCL diagnosis, while the risks for esophageal, sigmoid colon, vulvar, testicular cancers, and HL increased significantly after a latency period exceeding five years.
Conclusion:
Our study highlights the growing recognition of SPM in MCL, reinforcing the necessity for continuous vigilance. Awareness of the heightened risks of certain malignancies with certain demographic groups highlight the need for implementing targeted strategies. Furthermore, the median time of 5 years to SPM, also emphasizes the need to prioritize monitoring MCL patients' post-treatment. Additional research is essential to better understand the underlying mechanisms of this heightened risk, which could ultimately inform treatment approaches and mitigate the impact of second malignancies in this susceptible population..