Analysis of Cause of Death in Patients With Follicular Lymphoma in the Rituximab Era


Key Points

  • Lymphoma was the most common cause of death over 10 years.
  • Treatment-related mortality was also a prominent cause of death.

In a pooled analysis of French and U.S. follicular lymphoma cohorts reported in the Journal of Clinical Oncology, Sarkozy and colleagues found that lymphoma was the most common cause of death during the first decade of the rituximab era in treatment of the disease.

The study involved data from newly diagnosed patients with follicular lymphoma grade 1–3A enrolled between 2001 and 2013 in two French referral institutions (n = 5,734, median follow-up = 89 months) and between 2002 and 2012 in the University of Iowa and Mayo Clinic Specialized Program of Research Excellence (n = 5,920, median follow-up = 84 months). Cause of death (COD) was classified as resulting from lymphoma, other malignancy, treatment-related death, or all other causes.

Causes of Death

Overall survival at 10 years was 80% in the French cohort and 77% in the U.S. cohort. Cause of death was determined in 248 (88%) of 283 deaths. In the pooled cohort, the 10-year cumulative incidence of death by cause was 10.3% for lymphoma, 3.0% for treatment-related mortality, 2.9% for other malignancy, 2.2% for other causes, and 3.0% for unknown cause.

The 10-year cumulative incidence of death from lymphoma or treatment was higher vs death resulting from all other causes for:

  • Each age group, including patients aged ≥ 70 years at diagnosis (25.4% vs 16.6%)
  • Patients with a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3 to 5 (27.4% vs 5.2%), but not FLIPI score of 0 to 1 (4.0% vs 3.7%)
  • Patients who failed to achieve 24-month event-free survival (36.1% vs 7.0%), but not for patients who achieved 24-month event-free survival (6.7% vs 5.7%)
  • Patients with a history of transformed follicular lymphoma (45.9% vs 4.7%), but not patients without such history (8.1% vs 6.2%).

In total, 77 (55%) of 140 deaths due to lymphoma occurred in patients with follicular lymphoma transformation after diagnosis.

The investigators concluded, “Despite the improvement in overall survival in patients with follicular lymphoma in the rituximab era, their leading [cause of death] remains lymphoma, especially after disease transformation. Treatment-related mortality also represents a concern, which supports the need for less toxic therapies.”

Gilles Salles, MD, of the Hospices Civils de Lyon, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Institutes of Health grants. The study authors’ full disclosures can be found at

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