Prior Malignancy Linked to Risk of Secondary Malignancy in Follicular Lymphoma

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Previous research has found a link between a prior malignancy and secondary primary malignancy risk in patients with multiple myeloma. A new study suggests a similar association in follicular lymphoma.

Patients with follicular lymphoma (FL) who have a prior malignancy diagnosis (PMD) face a greater risk of secondary primary malignancy (SPM) and death, new data suggest, although the increased risk may be linked with the therapy chosen for the initial malignancy.

A team of Dutch researchers came to that conclusion following an analysis of a national database of more than 8000 patients who were diagnosed with FL over a nearly 2-decade period. Their findings were published in the European Journal of Haematology.1

The treatment landscape, and thus prognosis, for patients with FL has significantly improved since the introduction of rituximab (Rituxan) and other therapies. As a result, patients with FL are living longer, though some evidence has suggested that these patients might face a higher risk of SPM, including hematological malignancies such as Hodgkin lymphoma and acute myeloid lymphoma, and solid tumors including stomach, lung, and kidney/pelvis cancer.

A previous Swedish study2 of patients with multiple myeloma found an association between PMD and SPM and mortality. Those findings suggested that genetic susceptibility might be a factor for such patients. However, the evidence of a PMD’s impact on patients with FL has thus far been limited.

Hoping to change that, corresponding author Avinash G. Dinmohamed, MSc, PhD, of the Netherlands Comprehensive Cancer Organization, and colleagues, analyzed the Netherlands Cancer Registry to locate 8028 adult patients who were diagnosed with grades 1-3B FL from 1994 through 2012. The study included a follow-up period through 2017.

Of the 8028 patients, 6% (483 patients) had a prior malignancy. Of those, 17.2% (83 patients) developed an SPM. That compared with an SPM rate of 13.6% among the 1,023 patients who did not have a PMD. The median time between the PMD and the FL diagnosis was 5.3 years for patients who had an SPM and 5.4 years for patients without an SPM.

Patients with a PMD had an SPM subdistribution hazard ratio (SHR) of 1.30 (95% CI). The risk was especially high for carcinomas of the respiratory tract (SHR, 1.83) and cutaneous squamous cell carcinomas (SHR, 1.58). They also faced a higher risk of death (HR, 1.43; 95% CI).


However, the investigators also noticed a link between prior treatment and risk of SPM. They noted that patients with a PMD could experience prolonged immune dysfunction as a result of their prior treatment, and systemic therapy and/or radiotherapy could have a carcinogenic effect based on the dose. That effect could be compounded with treatment for FL.

“Thus, whenever a PMD was treated with systemic therapy and/or radiotherapy, the cumulative dose of potential carcinogens was likely higher for patients with a PMD, as compared to those without a PMD, due to prior cancer therapy,” they wrote.

Looking at mortality specifically, the authors found a heightened risk only among patients with a PMD who were treated with systemic therapy and/or radiotherapy.

“This finding might be explained by the (late) effects from the prior systemic therapy and/or radiotherapy, potentially leading to organ dysfunction, cardiovascular disease, and death,” they wrote.

Taken together, the authors said their findings need to be aware of the risk of SPMs in patients with FL, especially if the patient has a PMD and was treated with systemic therapy and/or radiotherapy.


  1. Dinnessen, MA,Visser, O,Tonino, SH, et al.The impact of prior malignancies on the development of second malignancies and survival in follicular lymphoma: a population‐based study. eJHaem. Published online October 8, 2020. doi: 10.1002/jha2.108​
  2. Jonsdottir G, Lund SH, Bjorkholm M, Turesson I, Hultcrantz M, Porwit A, et al. The impact of prior malignancies on second malignancies and survival in MM patients: a population‐based study. Blood Adv. 2017;1(25):2392‐98