TOPLINE:

In a population-based study, the progression of disease after first-line therapy was associated with a more than sevenfold increased risk for mortality in patients with mantle cell lymphoma (MCL), and progression occurring after 6 years was associated with a more than twofold higher risk for mortality than no progression.

METHODOLOGY:

• Researchers analysed data of 1186 patients with MCL (median age, 70 years; 26.1% women) from the Swedish Lymphoma Register who were diagnosed between 2006 and 2018 and received systemic first-line treatment.
• Patients were categorised into three groups on the basis of the first-line treatment regimen: those on bendamustine and rituximab (BR; 33%), the Nordic MCL2 regimen (30%), and R-CHOP (rituximab + cyclophosphamide, doxorubicin hydrochloride [hydroxydaunomycin], vincristine [Oncovin], prednisone; 14%).
• Patients were followed up from the date of the initiation of the first-line treatment until death, the end of the study, or 10 years after the start of initial therapy, whichever occurred first.
• Outcomes included the effect of the progression of disease on all-cause mortality and overall survival on the basis of the timing of progression and the first-line treatment.

TAKEAWAY:

• At a median follow-up of 3.7 years, almost half of patients (48%) experienced progression of disease; within 2 years, 24.2% of patients treated with BR, 18.9% treated with the Nordic MCL2 regimen, and 35.6% treated with R-CHOP experienced progression.
• Overall, patients with progression of disease had significantly higher all-cause mortality (adjusted hazard ratio [aHR], 7.56; 95% CI, 6.32-9.05). Those with progression within the first year showed nearly ninefold higher mortality (aHR, 8.83; 95% CI, 7.15-10.9) and those with progression after 6-10 years of treatment exhibited more than twofold higher mortality (aHR, 2.67; 95% CI, 1.05-6.79) than those without progression.
• Treatment-specific analysis revealed the strongest negative effect of late progression in patients treated with BR (aHR, 5.58; 95% CI, 1.69-18.5) and early progression in those treated with Nordic MCL2 (aHR, 36.8; 95% CI, 22.6-59.9).
• The median overall survival, regardless of the timing of progression, was 1.49 years. The rates of 1- and 5-year overall survival were 33.9% and 7.3% within 1 year of progression, 65.6% and 15.5% within 1-2 years, 77.4% and 33.3% within 2-4 years, and 86.3% and 34.0% within 4-6 years, respectively, and the rate of 1-year overall survival was 83.9% within 6-10 years of progression.

IN PRACTICE:

"This study underscores the strong negative impact of progression on overall survival in MCL, demonstrating that all events of disease progression — even those occurring up to 10 years post treatment — are associated with inferior survival," the authors wrote, adding that "efforts should focus not only on prolonging remission durations but also on avoiding progression/relapse altogether."

SOURCE:

This study was led by Sara Ekberg, Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. It was published online on November 05, 2025, in the International Journal of Cancer.

LIMITATIONS:

This study lacked information on specific molecular markers such as TP53 mutation or p53 status, histologic subtype, and Ki-67, limiting the ability to fully characterise the genetic heterogeneity of MCL and its influence on disease progression. Additionally, detailed information on relapse treatments, including Bruton tyrosine kinase inhibitors and chimeric antigen receptor T-cell therapy brexucel, was limited during the study period.

DISCLOSURES:

This study was funded by a grant from the Swedish Cancer Society and Åke Wiberg Foundation. One author reported receiving research support to the department from Takeda and educational boards with finance to the department from Janssen Cilag, AbbVie, and Kite/Gilead. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.