Survival remains limited in older transplant-ineligible mantle cell lymphoma

Among older adults in Ontario who were ineligible for autologous stem cell transplantation, real-world survival with mantle cell lymphoma was limited, particularly after relapse, according to a population-based observational study of 754 patients diagnosed between 2013 and 2021. Most received first-line bendamustine and rituximab, while ibrutinib dominated second-line treatment, yet many patients died before progressing to another regimen. Median overall survival was 3.51 years after first-line therapy began, falling to 0.60 years after second-line treatment and 0.43 years after third-line treatment.

Mantle cell lymphoma is a rare and aggressive form of non-Hodgkin lymphoma that often begins with slow growth in lymph nodes before progressing to rapid growth and widespread disease. Diagnosis frequently occurs at an advanced stage, potentially involving the gastrointestinal tract, spleen, and bone marrow, and most patients are diagnosed between 60 and 70 years of age. The retrospective study used linked Ontario health administrative records from the Institute for Clinical Evaluative Sciences, including data from the Ontario Cancer Registry, to examine patients who were at least 65 at diagnosis and had not received an autologous stem cell transplant.

Among the 754 included patients, the median age was 76 years, with an interquartile range of 71 to 82, and 56.4% were at least 75. Men represented 71.1% of the cohort, and 22.4% of patients with recorded collaborative staging had Stage IV disease at diagnosis. Collaborative stage was missing for 64.1% of the cohort, so the available stage distribution does not describe the entire population. Mean follow-up was 36.1 months, with a standard deviation of 31.1 months. The analysis excluded patients younger than 65, those who received an autologous stem cell transplant, and those with incomplete or invalid administrative records. The design therefore describes a population generally considered ineligible for intensive chemotherapy and transplantation in Ontario practice, rather than directly measuring the clinical decision for every individual participant.

Annual diagnoses remained relatively steady, ranging from 76 to 91 new cases between 2013 and 2021. As Ontario’s population aged 65 and older increased, the estimated crude incidence fell from 0.0425 cases per 1,000 people in 2013 to 0.0332 per 1,000 in 2021. The 2013 estimate had a 95% confidence interval of 0.0344 to 0.0524 per 1,000, while the 2021 estimate had an interval of 0.0269 to 0.0408. This pattern describes a population-rate change over the study period rather than a demonstrated reduction in the underlying number of new diagnoses. The retrospective design could not establish why the rates changed, and the confidence intervals overlapped across annual estimates.

Systemic treatment was initiated in 540 patients, or 71.6% of the cohort, while 214 received no systemic therapy during follow-up. Among treated patients, 391 received only first-line therapy, 125 received second-line therapy without a third line, and 24 reached third-line treatment. Bendamustine plus rituximab was the most common first-line regimen, used in 414 patients, or 76.7% of those treated. R-CHOP accounted for 10.0%, R-CVP for 4.3%, and other first-line regimens for 7.6%. Rituximab maintenance after first-line induction was given to 277 patients, representing 51.3% of the treated group, while 168 patients, or 22.3% of the full cohort, received local radiotherapy. Because these were descriptive counts, the study did not test whether the use of maintenance rituximab improved survival.

The first-line regimen was generally initiated soon after diagnosis: median time from diagnosis to treatment was 1.64 months, with an interquartile range of 0.99 to 3.88 months. Median recorded treatment duration was 12.8 months for patients receiving rituximab maintenance and 4.70 months for those without maintenance. Among the 149 patients who received second-line treatment, ibrutinib was used in 109 cases, or 73.2%, and bortezomib-based therapy in 8, or 5.4%. Median time from diagnosis to second-line treatment was 21.6 months, with an interquartile range of 11.1 to 38.9 months. Recorded second-line treatment lasted a median of 2.14 months, including 2.07 months for ibrutinib. These durations represent the interval between the first and last recorded treatment within each line and do not by themselves establish why treatment ended.

Following first-line treatment, 212 patients died before beginning second-line therapy, accounting for 39.3% of those receiving first-line systemic treatment. Of the 149 patients who reached second-line treatment, 102 died before third-line treatment, or 68.5%. Seven of the first-line deaths were classified as COVID-19-related, as were six deaths after second-line treatment. The investigators estimated median time to next treatment or death at 2.62 years, with a 95% confidence interval of 2.24 to 3.01 years. Patients whose first-line treatment was bendamustine plus rituximab had the longest estimated time to next treatment or death, at 2.85 years with a 95% confidence interval of 2.54 to 3.62, compared with 1.74 years for R-CHOP and 0.90 years for R-CVP. These unadjusted comparisons describe observed outcomes and do not establish that any regimen caused the differences.

Median overall survival after first-line treatment initiation was longest among patients receiving bendamustine plus rituximab, at 4.02 years with a 95% confidence interval of 3.23 to 4.72, compared with 2.67 years for R-CHOP, whose confidence interval was wide at 1.52 to 5.17 years. Median survival across all first-line treatments was 3.51 years, with a 95% confidence interval of 2.89 to 4.03. Age was associated with survival: patients aged 65 to 74 had a median of 5.95 years after first-line treatment, with a 95% confidence interval of 4.26 to 8.01, whereas those aged 75 or older had a median of 2.49 years, with an interval of 2.11 to 2.82. In second-line treatment, median survival was 0.50 years for ibrutinib and 0.60 years across all second-line regimens. Because the study was retrospective and unadjusted, differences cannot be attributed solely to age, regimen selection, disease severity, comorbidity, or other clinical factors.

The findings also illustrate how administrative data were used to assess outcomes in a population with limited treatment options. Progression-free survival could not be measured reliably because health administrative records do not consistently capture progression, so time to next treatment or death served as a pragmatic surrogate. This endpoint combines subsequent treatment with death and therefore differs from progression-free survival. Censoring at the end of the study may have limited assessment of patients diagnosed near 2021, and Ontario-specific funding and clinical practices may limit generalizability to other provinces. Administrative data also may not capture every treatment delivered through compassionate programs, although the investigators expected that omission to have little effect on the analysis. The linked population-level data nevertheless captured nearly all registry-diagnosed cases, providing a broad view of care delivered in routine practice. The study identifies an unmet need for more effective treatments for older patients with mantle cell lymphoma who are ineligible for autologous stem cell transplantation.

Subject of Research: Real-world treatment patterns and survival in older transplant-ineligible mantle cell lymphoma patients in Ontario

Article Title: Real‐World Treatment Patterns, Burden of Illness, and Survival of Autologous Stem Cell Transplant‐Ineligible Patients With Mantle Cell Lymphoma in Ontario, Canada

Article References: George, S., Seung, S. J., Thibault, S., Wong, A., Hamilton, M. A., & Prica, A. (2026). Real‐World Treatment Patterns, Burden of Illness, and Survival of Autologous Stem Cell Transplant‐Ineligible Patients With Mantle Cell Lymphoma in Ontario, Canada. eJHaem, 7(5), Article e70384. https://doi.org/10.1002/jha2.70384

Image Credits: AI Generated

DOI: 10.1002/jha2.70384

Keywords: mantle cell lymphoma, Ontario, older adults, autologous stem cell transplant, ibrutinib, bendamustine, rituximab, real-world evidence, population-based study, overall survival, Real, World