Even years after initial treatment, the persistence of mantle cell lymphoma (MCL) can significantly impact a patient’s survival, according to a recent population-based study from Sweden. The findings, which challenge conventional thinking about the timing of disease progression, suggest that relapses occurring more than six years after initial treatment carry a substantial risk of mortality.
Researchers led by Dr. Sara Ekberg of the Karolinska Institutet in Stockholm analyzed data from the Swedish lymphoma registry, following 1186 patients diagnosed with MCL between 2006 and 2018 for up to 10 years. The data were initially presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2025 and are scheduled for full publication in the International Journal of Cancer in April 2026.
The study categorized patients into different treatment groups. Approximately 33% received bendamustine rituximab (BR), 30% received a Nordic MCL2 regimen – consisting of dose-escalated R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) alternating with R-cytarabine, followed by high-dose treatment with autologous stem cell transplantation – and 14% received R-CHOP or similar therapies. Other regimens, including chlorambucil and R-CHOP/cytarabine, as well as ibrutinib alone, were also included, though numbers were insufficient for separate analysis. Some patients also received maintenance treatment with rituximab.
While it’s long been understood that early disease progression within the first 24 months of treatment is particularly detrimental, this new research demonstrates that progression occurring six to ten years after initial treatment also carries a significantly worse prognosis. Patients experiencing this later relapse showed more than a 2.67-fold increased risk of mortality.
“Our results clearly emphasize large survival benefits of late [disease progression] over early [disease progression] in all treatment groups,” the authors wrote, “and even better prognosis if [disease progression] can be avoided altogether.” The study highlights that survival differences persisted for up to nine years after primary treatment.
Specifically, among patients treated with BR who progressed at the six-year mark, only 38% were alive five years later, compared to 77% of those who remained progression-free – a 39% survival deficit. For patients receiving the Nordic MCL2 regimen, the gap was 26% (62% vs. 88%).
The impact of disease progression varied depending on the treatment received. The Nordic MCL2 regimen was associated with the most dramatic difference, with patients progressing within 12 months experiencing a 37-fold increased mortality risk. This likely reflects a more aggressive disease course in patients who didn’t respond to intensive therapy. However, even among those progressing after six to ten years, BR-treated patients faced a substantial 5.6-fold increase in relative risk, while those on the Nordic MCL2 regimen also experienced a significant effect.
These findings have important implications for how MCL is managed. The authors emphasize the importance of not only prolonging remission but also preventing relapse entirely. They suggest that all progression events – regardless of when they occur – are clinically significant and should inform treatment decisions.
The study also underscores the potential value of maintenance therapy in preventing progression and calls for further investigation into the use of Bruton tyrosine kinase (BTK) inhibitors, potentially in combination with other therapies. Combining rituximab with BTK inhibitors may lead to deeper, more durable remissions.
Several ongoing clinical trials are exploring novel approaches to MCL treatment. The BOVen study (NCT03824483) is evaluating zanbrutinib, obinutuzumab, and venetoclax for newly diagnosed patients with TP53-mutated MCL, showing a 2-year progression-free survival rate of 72%. Preliminary results from the TrAVeRse study (NCT05951959) investigating acalabrutinib, venetoclax, and rituximab demonstrate high rates of minimal residual disease negativity. The BRUIN study (NCT03740529) has shown promising 5-year data for pirtobrutinib in relapsed or refractory MCL patients.
Balancing Efficacy With Long-Term Effects
The authors acknowledge that intensifying treatment, including with BTK inhibitors, must be carefully balanced against potential adverse effects, such as late toxicities and the risk of secondary malignancies, requiring lifelong follow-up. Their analysis revealed that 46% of patients over 65 years of age died from MCL within five years (30% after disease progression), highlighting the importance of addressing the underlying disease despite potential treatment-related risks.
The treatment landscape for MCL is rapidly evolving, with options including BTK inhibitors and chimeric antigen receptor (CAR) T cell therapy, such as brexucabtagene autoleucel. Immunochemotherapy remains the standard of care for first-line treatment globally, but further research into alternative strategies is warranted.
“Efforts should focus not only on prolonging remission durations but also on avoiding progression/relapse altogether,” the authors conclude. “Future research should continue to explore the evolving treatment landscape and the role of maintenance therapies, and further elucidate the molecular factors influencing disease progression and overall survival in MCL.”
References
- Ekberg S, Glimelius I, Albertsson-Lindblad A, Smedby KE, Jerkeman M, Dietrich CE. Disease progression more than 6 years after treatment impacts overall survival in mantle cell lymphoma. Int J Cancer. 2026;158(7):1836-1845. Doi:10.1002/ijc.70220
- Wang M, Jurczak W, Trneny M et al. Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2025;26(2):200-213. Doi:10.1016/S1470-2045(24)00682-X
- Kumar A, Soumerai J, Abramson JS, et al. Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation. Blood 2025;145(5):497-507. Doi:10.1182/blood.2024025563
- Kumar A. Preliminary safety and efficacy of BOVen (zanubrutinib, obinutuzumab, and venetoclax) as frontline therapy for older patients with mantle cell lymphoma. Presented at: 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; Orlando, FL. Oral abstract 888.
- Wang CM, Cohen J, Shah N, et al. Pirtobrutinib in relapsed/refractory (R/R) mantle cell lymphoma (MCL): final update from the phase 1/2 BRUIN study. Blood. 2025;146(suppl 1):Abstract 665. Doi:10.1182/blood-2025-665
- A study of acalabrutinib plus venetoclax and rituximab in participants with treatment naïve mantle cell lymphoma (TrAVeRse). ClinicalTrials.gov. Updated October 21, 2025. Accessed December 29, 2025. https://www.clinicaltrials.gov/study/NCT05951959
- Wojtowicz MM, Hawkes E, Romejko-Jarosinska J, et al. Acalabrutinib plus venetoclax and rituximab in patients with treatment-naïve mantle cell lymphoma (MCL): results from the phase 2 TrAVeRse study. Presented at: 67th American Society of Hematology Annual Meeting & Exposition; December 6-9, 2025; Orlando, FL. Paper 0884.
