Disease progression within 24 months of frontline chemoimmunotherapy (POD24) was highly predictive of poor prognosis in patients with follicular lymphoma (FL). In a study published in Blood, researchers led by Carla Casulo, MD, of the University of Rochester in New York, found that risk factors for POD24 in patients with FL include male sex, poor performance status, high risk Follicular Lymphoma International Prognostic Index (FLIPI) score, and elevated beta-2 microglobulin (B2M).
According to the researchers, the findings were derived from the largest data set published to date and validate POD24 as a “robust marker” of poor overall survival (OS) in a widely heterogeneous group of patients with FL. Likewise, the investigators noted that the identified well-defined clinical factors for FL-related prognosis in the study may aid in “building comprehensive prognostic models in the future that incorporate clinical and molecular predictors of POD24,” thus improving risk stratification and more appropriate management.
The study relied on data from 5,225 previously untreated patients with FL from 13 international randomized controlled trials that studied active treatment. Researchers evaluated the association between POD24 and FLIPI risk category, sex, B2M, and performance status (PS) in logistic regression models. Additionally, Cox regression was used to evaluate the association between POD24 and OS.
Ten induction and three maintenance randomized controlled trials were analyzed. In the pooled cohort of 5,225 patients, approximately 29% progressed and 2.5% died within a 24-month period of trial registration. The majority of patients (62.5%) received anthracyclines, and more than half (53.2%) were treated with rituximab.
At 24 months, patients without progression more frequently had favorable PS, limited stage, low-risk FLIPI score, normal baseline hemoglobin, and normal baseline B2M.
In the logistic regression model for POD24, variables associated with an increased risk of disease progression before 24 months included:
- male sex (odds ratio [OR] = 1.30; 95% CI 1.14-1.47; p<0.01)
- PS ≥2 (OR=1.63; 95% CI 1.27-2.10; p<0.01)
- Intermediate-risk FLIPI score (OR=1.58; 95% CI 1.28–1.94; p<0.01) or high-risk FLIPI score (OR=2.94; 95% CI 2.41–3.59; p<0.01)
In an analysis that was adjusted for sex and stratified by PS and FLIPI, there was a significant association between POD24 and poor subsequent OS (hazard ratio [HR] = 4.85; 95% CI 4.32-5.45; p<0.01). There was also a significant association between POD24 and poor OS in patients treated with rituximab induction chemotherapy (HR=5.39; 95% CI 4.40-6.61; p<0.01). The impact of POD24 was also observed in patients treated with induction chemotherapy without rituximab (HR=4.26; 95% CI 3.68-4.93; p<0.01), as well as patients treated with rituximab at induction without chemotherapy (HR=6.57; 95% CI 2.64-16.32; p<0.01).
According to a landmark OS analysis of patients alive at 24 months, the three- and five-year survival probabilities in patients with progressive disease within the first 24 months were 86.8% and 71.2%, respectively. In patients who were progression-free at 24 months, the three-year survival probability was 98.5% and the five-year survival probability was 93.6%.
A multivariable Cox model adjusted for sex and stratified by PS and FLIPI demonstrated that disease progression within 24 months was significantly associated with poorer subsequent OS (HR=3.03; 95% CI 2.65-3.47; p<0.01).
Study authors report relationships with Celgene and Roche, which funded the study.
Reference
Casulo C, Dixon JG, Le-Rademacher J, et al. Validation of POD24 as a robust early clinical endpoint of poor survival in FL from 5,225 patients on 13 clinical trials [published online ahead of print, 2021 Oct 6]. Blood. doi: 10.1182/blood.2020010263.
