Impact of Histologic Transformation on Prognosis in Early Relapsing Follicular Lymphoma

By Julie Gould - Last Updated: December 12, 2024

Patients with follicular lymphoma (FL) experiencing early progression or death within 24 months (POD24) after immunochemotherapy face poor outcomes, with histologic transformation (HT) further compounding their prognosis, according to data presented at the 66th American Society of Hematology Annual Meeting & Exposition. Researchers conducted a multicenter study aimed to evaluate survival outcomes for patients with POD24, stratified by retained FL histology (POD24_FL), biopsy-proven HT to aggressive lymphoma (POD24_HT), or indeterminate biopsy status (POD24_I).

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From a cohort of 1,122 patients with FL, 308 with POD24 were identified. The median age at POD24 was 58 years, and most (76%) were non-Hispanic White individuals. Patients had received first-line treatments including R-CHOP (45%), bendamustine plus rituximab (33%), and rituximab plus cyclophosphamide, vincristine, and prednisone (21%). Biopsy at POD24 revealed that 52% had retained FL histology, 17% had HT, and 30% had indeterminate or no biopsy findings.

Survival analyses showed significantly worse overall survival (OS) for patients with POD24_HT  compared with those with POD24_FL, with a hazard ratio of 3.79. Five-year OS for patients with POD24_HT was 31% versus 71% for those with POD24_FL. Notably, patients with POD24_I had outcomes comparable to those with POD24_FL (5-year OS, 75% vs 71%). Event-free survival (EFS) followed a similar pattern, with patients with POD24_HT demonstrating a 2-year EFS of 10% compared with 27% for patients with POD24_FL.

At the time of POD24, second-line treatment strategies varied. Intensive salvage chemotherapy and autologous stem cell transplantation were more common among patients with POD24_HT, but their survival remained significantly worse. Despite aggressive treatment, the 5-year probability of lymphoma-related death was 53% among patients with POD24_HT, compared with 20% among patients with POD24_FL. This suggests that HT is a critical driver of poor prognosis, but not the sole factor because even patients with retained FL histology had suboptimal outcomes.

This study underscored the heterogeneity within the POD24 population. Although HT accounts for a significant disparity in survival, the broader poor outcomes of patients with POD24 highlight an urgent need for targeted research and innovative therapies.

“In our multicenter cohort, we identified remarkable differences between the two biopsy-demonstrated entities of POD24 (ie, with and without HT),” the study authors explained.

“Despite most patients receiving appropriate aggressive treatment, those with POD24_HT represent a distinctly vulnerable population warranting further study in directed prospective studies of both FL biology and clinical trials.”

Reference: Casulo C, Larson MC, Ray JR, et al. Outcomes in early relapse of follicular lymphoma versus early histologic transformation following firstline immunochemotherapy in follicular lymphoma. Abstract #1652. Presented at the ASH Annual Meeting; December 7-10, 2024; San Diego, California.

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