Lymphoma Still Top COD in Patients During Rituximab Era

Despite improved outcomes seen in the rituximab era, the leading cause of death in patients with follicular lymphoma during the first decade remains lymphoma, according to the results of a pooled analysis published in The Journal of Clinical Oncology.

Other causes of death, occurring less than one-third as often, included treatment-related mortality, other malignancies, other causes, or unknown causes.

“Despite a favorable 10-year overall survival, lymphoma represents the leading cause of death in the first decade after diagnosis,” wrote Clementine Sarkozy, of Hospices Civils de Lyon, France, and colleagues. “This is particularly true for patients who present with high FLIPI (Follicular Lymphoma International Prognostic Index) score, for those with transformed disease, and for those who did not achieve event-free survival within 12 months or event-free survival within 24 months.”

To gather data on cause of death in patients with follicular lymphoma, Sarkozy and colleagues pooled information from two cohorts of patients with newly diagnosed disease grade 1–3a. The first was a French cohort that included 734 patients with a median follow-up of 89 months. The second was a US cohort that included 920 patients with a median follow-up of 84 months.

The 10-year overall survival was similar between the two groups at about 80%. Of patients who died, the researchers were able to classify the cause of death in 88%.

At 10 years, lymphoma was the cause of death in 10.3% of patients. The next most common causes were treatment-related mortality (3.0%), other malignancy (2.9%), other causes (2.2%), or unknown cause (3.0%). Lymphoma as a cause of death was slightly higher in the French cohort than the US cohort (65% vs 50%), but outcomes were similar when based on the use of cumulative incidence with competing risk of death.

In addition, the 10-year cumulative incidence of death from lymphoma or its treatment was higher than death as a result of all other causes among all age groups analyzed, including those patients aged 70 or older. This was also true for patients with a FLIPI score of 3 to 5 (27.4% vs 5.2%, respectively), for patients who did not achieve event-free survival within 24 months (6.7% vs 5.7%), and for patients with a history of transformed follicular lymphoma (45.9% vs 4.7%).

“This important notion that transformation in follicular lymphoma is the major cause of lymphoma-related death should provide a framework for future specific approaches,” the researchers wrote.

The researchers acknowledged one limitation of the study was that “management strategies (e.g., surveillance, retreatment, and repeat biopsy) were not protocol driven but were at the discretion of the managing physician, and the effect of this on cause of death is unknown.”

Commenting on the results of this article, Oliver Weigert, MD, of Ludwig Maximilian University of Munich, congratulated his French and US colleagues on this large and important study.

"Among the many interesting observations, my take-home message is that despite recent advances in the treatment of patients with FL, there is still need for improvement," Weigert told Cancer Network.

"As lymphoma remains the major cause of death, clearly more efficient therapies are needed. At the same time, as treatment-related mortality ranks second among the causes of death, less toxic therapies are needed, especially for older patients and patients with comorbidities," he said. "Essentially, this is a wake-up call to develop individualized treatment approaches. Time is up for all-comer strategies ('one-size fits all'), and we should aim to stratify patients by individual risk and/or disease biology."