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Outlining Incidence Trends and Disparities of MZL

February 14, 2025
By ONCOLOGY Staff
Publication
Article
OncologyONCOLOGY Vol 39, Issue 1
Volume 39
Issue 1
Pages: 21-22

Potential contributing factors of marginal zone lymphoma (MZL) were highlighted in a recent discussion with James R. Cerhan, MD, PhD.

Potential contributing factors of marginal zone lymphoma (MZL) were highlighted in a recent discussion with James R. Cerhan, MD, PhD.

Potential contributing factors of marginal zone lymphoma (MZL) were highlighted in a recent discussion with James R. Cerhan, MD, PhD.

James R. Cerhan, MD, PhD, discussed the latest trends in marginal zone lymphoma (MZL) epidemiology in the US, including drawing on data from the Surveillance, Epidemiology, and End Results (SEER) database. He previously presented these findings at the 2024 MZL Workshop hosted by the Lymphoma Research Foundation.

While overall MZL incidence has been stable, rates have been increasing among women for splenic MZL according to Cerhan, a professor of epidemiology at the Mayo Clinic College of Medicine and Science, Ralph S. and Beverly Caulkins Professor of Cancer Research, Enterprise Deputy Director for Population Science and Cancer Control in the Mayo Clinic Comprehensive Cancer Center, and Associate Director of the Mayo Clinic Cancer Registry.

Cerhan also highlighted how age-adjusted incidence is higher in patients who are non-Hispanic White compared with other racial and ethnic groups, which is potentially linked to higher rates of infections like hepatitis C and autoimmune diseases in this population. The discussion calls attention to the need for further research to understand the factors driving these trends and to develop prevention strategies.

Q / Is MZL becoming more common in the US?

Cerhan / When we look at the Surveillance, Epidemiology, and End Results Program (SEER) data in the US from 2001 to 2021, that’s what we reported at the [MZL Workshop] meeting. The number of newly diagnosed cases is going up, but after accounting for the age of the population and size, the age-adjusted incidence for MZL is fairly stable, maybe a slight increase, but nothing statistically significant. When we think of MZL, this was also true for nodal and extranodal subtypes. In contrast, we see about a 1% per year increase in the incidence [of MZL], and most of that is occurring in women. We are seeing a little bit of an increase, but nothing dramatic.

Q / Your presentation highlighted differences in MZL incidence across different demographic groups. What are the potential underlying factors contributing to these disparities, and how can we address them?

Cerhan / The incidence of MZL increases strongly with age. It’s similar in men and women, and, overall, it’s higher in patients who are non-Hispanic White relative to [those who are] African American, Hispanic, or Asian and Pacific Islander. This pattern for age and race/ethnicity holds for the main MZL subtypes. However, nodal MZL is more common in men, splenic is more common in women, and [the incidence is] similar for extranodal. We don’t understand this variation, but some of the leading risk factors for MZL are infections, including hepatitis C and having a history of autoimmune disease. We know both these risk factors are more common in patients who are White compared with other racial and ethnic groups and have been increasing in the US population. Additionally, autoimmune diseases are much more common in women than men. This might explain some of the increase in splenic MZL, particularly in non-Hispanic White women.

Q / There has been much media attention on an increasing incidence of cancers diagnosed before the age of 50 years. Are we seeing this in MZL?

Cerhan / Looking at the US SEER data, we do not see any significant increase in the incidence in the under-age 50 group with the MZL subtypes. However, we are seeing a statistically significant increase in extranodal MZL, no change in nodal, and perhaps a small decline in the incidence of splenic, which contrasts with what we’re seeing overall. This is now just in the under-50 [group], the increase in MZL; extranodal MZL was much greater in women, particularly for the extranodal sites of the skin and perhaps the lung. We don’t understand the reasons for these patterns yet.

Q / What about US survival rates for patients with MZL?

Cerhan / The most recent relative US survival rates and relative survival accounts for competing risk of dying as you age are quite high currently in the US, at 92%. They’re a bit lower for nodal and splenic at 85% and a bit higher for extranodal at 96%, interestingly. Unlike the patterns we see for incidence, these survival rates are quite similar for men and women and by race and ethnicity, and they’ve been slowly getting better since 2001, but they are quite high.

Q / Do patients with MZL mainly die of their lymphoma or with their lymphoma?

Cerhan / Keeping in mind that overall survival is quite high, patients with MZL are a bit more likely to die of non-lymphoma causes than dying of their lymphoma. This distinction gets even stronger as you go into older age groups. One interesting recent finding is that newly diagnosed patients with MZL who have a relapse, a progression, or need treatment within 2 years of their diagnosis are subsequently more likely to die of their lymphoma while those patients who go 2 years without any of these events may be dying of other causes, not due to their lymphoma.

Q / How do MZL risk factors cluster with other non-Hodgkin lymphoma subtypes, and what are the implications of this finding for our understanding of MZL pathogenesis?

Cerhan / MZL is very similar to the other common lymphoma subtypes in that they share some of the risk factors, but they also tend to have some distinct associations. Family history, for example, is an established risk factor as it is for all other lymphoma subtypes, and they have the same strength of risk. From a genetics perspective, it looks like MZL is more strongly correlated with some subtypes, like chronic lymphocytic leukemia and diffuse large B-cell lymphoma, compared with, say, follicular lymphoma.

Infectious agents tend to be unique to MZL or certain MZL subtypes. A Helicobacter pylori infection and gastric MZL are often called MALT lymphoma. However, I can counter that right away with the hepatitis C virus, which is the most strongly associated with MZL, but we see it in multiple other lymphoma subtypes as well. Autoimmune disease is a driver of MZL. Again, we do see this shared with some other lymphoma subtypes, particularly diffuse large B-cell lymphoma. Studying these patterns provides us with some insights into etiology, and what’s coalescing around factors related to MZL looks like factors related to the immunologic status of the host. Immune suppression along with antigenic stimulation, be that an infectious agent or an autoimmune disease, seems to be particularly important for MZL.

Q / What are the most pressing research questions in MZL epidemiology that must be addressed to further improve our understanding of this disease?

Cerhan / In terms of causes of MZL, some newer risk factors require additional study, including smoking, alcohol use, sun exposure, and physical activity in certain occupations, as we have better tools to identify pathogens. This should be pursued, particularly for extranodal MZL. There could be some new findings there. In terms of outcomes after MZL diagnosis, it is important to be able to predict at diagnosis which treatments will fail patients early, that [is], an event within 24 months of their diagnosis, because then we could identify patients up front who need to have different treatments [because they] are not going to do well on their current standard. These are the patients you want to get on clinical trials as well as study their biology. We need to identify new treatment targets for those patients. However, for patients who go the 24 months without a relapse or progression and subsequently go on to die of other causes, you can reassure them and manage them with a low touch. You don’t need to be aggressive with them because they’re going to live out their life expectancy.

Q / Where do you see this field headed?

Cerhan / The integration of MZL epidemiology with MZL biology and immunology is going to accelerate, and that is going to give us some new mechanistic insights into how genetics and the environment impact the development of MZL. Hopefully, the reason to do that is to identify opportunities for prevention. The other big area that I see this field going [toward] is it is going to become more global, and studying populations with contrasting risk factors may help us identify new causes and new ways to prevent the disease.

Q / Is there anything you would like to add?

Cerhan / I want to acknowledge the Lymphoma Research Foundation for sponsoring the [MZL] workshop. It can bring [together] researchers from very different perspectives and give a deep dive into this disease, and now [we] have it published in ONCOLOGY.

Download Issue PDFDownload PDF
Articles in this issue

The Potential for Improved Processes, Outcomes, and Economics of Health Care
The Potential for Improved Processes, Outcomes, and Economics of Health Care
3 Things You Should Know About Adverse Events With Targeted Therapies for DLBCL
3 Things You Should Know About Adverse Events With Targeted Therapies for DLBCL
3 Things You Should Know About Identifying and Treating Epithelioid Sarcoma
3 Things You Should Know About Identifying and Treating Epithelioid Sarcoma
Advancing the MZL Landscape Through the MZL Workshop
Advancing the MZL Landscape Through the MZL Workshop
Pinpointing Ways to Overcome Challenges in MZL
Pinpointing Ways to Overcome Challenges in MZL
Outlining Incidence Trends and Disparities of MZL
Outlining Incidence Trends and Disparities of MZL
Highlighting Quality of Life Considerations for MZL Treatment
Highlighting Quality of Life Considerations for MZL Treatment
Creating a Collaborative Edge Through the MZL Workshop
Creating a Collaborative Edge Through the MZL Workshop
Nodal Marginal Zone Lymphoma and Its Diagnostic Challenges
Nodal Marginal Zone Lymphoma and Its Diagnostic Challenges
Insights, Knowledge Gaps, and Priorities in Marginal Zone Lymphoma Research
Insights, Knowledge Gaps, and Priorities in Marginal Zone Lymphoma Research
MZL Workshop Paves the Way for Better Treatment Options
MZL Workshop Paves the Way for Better Treatment Options
MZL Expert Insights Summit Sponsored by the Lymphoma Research Foundation
MZL Expert Insights Summit Sponsored by the Lymphoma Research Foundation
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