Early progression after BR is associated with high risk of transformation in advanced stage follicular lymphoma

Ciara L. Freeman, Robert Kridel, Alden A. Moccia, Kerry J. Savage, Diego R. Villa, David W. Scott, Alina S. Gerrie, David Ferguson, Fergus Cafferty, Graham W. Slack, Pedro Farinha, Brian Skinnider, Joseph M. Connors and Laurie H. Sehn

Key Points

  • Frontline bendamustine and rituximab in advanced stage follicular lymphoma has marked efficacy in this population-based analysis

  • Early progression within 24 months is associated with poor outcome after BR, however the majority of patients have transformed lymphoma


Despite widespread use of bendamustine and rituximab (BR) as frontline therapy for advanced stage follicular lymphoma (FL), little is known about the risk of early progression or incidence of histological transformation. We performed a retrospective analysis of a population-based cohort of 296 patients with advanced stage FL treated with frontline BR and maintenance rituximab. As previously demonstrated, outcomes with this regimen are excellent, with 2-year EFS estimated at 85% [95% CI 80-89%] and 2-year OS 92% (95% CI 88-95%). Progression of disease within 24 months (POD24) occurred in 13% of patients and was associated with a significantly inferior outcome with 2-year OS of 38% (95% CI 20-55%). The only significant risk factor for POD24 at baseline was elevated LDH (p<0.001). Importantly, the majority of POD24 patients (76%) had transformed disease. Compared to a historical cohort treated with RCVP, EFS has improved and the risk of POD24 has decreased, but a higher proportion of patients with POD24 harbor transformation. The overall incidence of transformation appears unchanged. The presence of occult or early transformation is the main driver of POD24 in FL patients treated with frontline BR. Identification of biomarkers and improved management strategies for transformation will be crucial to improving outcomes.

  • Submitted February 20, 2019.
  • Revision received July 11, 2019.
  • Accepted July 1, 2019.