Photo Credit: Pornpak Khunatorn
MCL patients with secondary malignancies have significantly shorter survival, particularly due to skin cancers and secondary leukemia.
One of the most serious late complications following lymphoma treatment is the development of second primary malignancies (SPMs). According to research presented at ASH 2024, previous large-scale studies conducted in Sweden and Denmark have confirmed an increased risk for SPMs in lymphoma survivors.
“The current study aimed to investigate the impact of SPMs on survival for patients with mantle cell lymphoma (MCL) relative to comparators with a similar malignancy,” the authors explained.
The study included all patients with MCL diagnosed from 2000 to 2020 in Denmark and from 2000 to 2017 in Sweden who later developed an SPM. These patients were matched in a 1:5 ratio with people from the general population who had a similar malignancy but no history of lymphoma. Matching criteria included birth year, sex, malignancy ICD-10 code, and calendar year of malignancy diagnosis. Patients and comparators were followed until death, emigration, or December 31, 2021 (2019 for Sweden).
Survival & Mortality in MCL Patients With SPM
Overall survival (OS) was estimated using the Kaplan-Meier method, and all-cause mortality hazard ratios (HRs) were calculated with adjustments for age, sex, and year of malignancy diagnosis. Pooled hazard ratios (pHRs) were computed using an inverse variance weighted method with a random effects model.
A total of 497 patients with MCL with an SPM and 1,992 matched comparators were analyzed. The median follow-up duration was 4.7 years for patients and 4.8 years for comparators. Most patients with MCL (71.5%) had stage IV disease at diagnosis, with 76.9% classified as intermediate or high risk based on the MCL International Prognostic Index. The primary treatment for MCL was chemoimmunotherapy (80%), with only 8% receiving radiotherapy.
The most common SPMs were skin cancer (45%), gastrointestinal cancer (12%), prostate cancer (12%), and lung cancer (12%). Secondary acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) was observed in 4% of patients. The median age at SPM diagnosis was 75 years. Mortality rates were high, with 54% and 59% of patients dying during follow-up in Denmark and Sweden, respectively. In Sweden, MCL was the leading cause of death (38%), followed by solid cancers (24%), non-malignant causes (20%), secondary leukemia/MDS (13%), and skin cancer (5%).
Effect of SPM on OS
Patients with an SPM had significantly shorter OS compared to matched comparators. The median OS for MCL patients with an SPM was 4.3 years in Denmark and 2.7 years in Sweden, whereas comparators had a median OS of 6.8 and 9.1 years, respectively. The pHR for all-cause mortality was 2.0 (1.1-3.6), with particularly high mortality for skin cancers (pHR 2.8, 1.8-4.5) and AML/MDS (pHR 2.4, 1.3-4.3). A trend in increased mortality was also observed for solid cancers (pHR 1.4, 0.8-2.5). OS varied by SPM type, with markedly worse survival for MDS/AML and skin cancers, particularly non-melanomas.
“Patients with MCL with an SPM have a compromised survival when compared to a background population with similar malignancies. The most common SPMs were skin cancers, which were associated with a higher likelihood of death, mostly driven by the underlying MCL,” the researchers concluded.
