Incorporating lymphopenia into the Follicular Lymphoma International Prognostic Index (FLIPI) can improve prognostication, according to researchers.
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The team added lymphopenia as a point in a revised FLIPI scoring system, called FLIPI-L, and found the new system could better predict overall survival (OS), progression-free survival, and histologic transformation in patients with follicular lymphoma.
George Yang, MD, of Moffitt Cancer Center in Tampa, Fla., and his colleagues described results with the FLIPI-L in a letter published in Blood Cancer Journal.
“Prior studies have demonstrated that lymphopenia was associated with worsened OS in [follicular lymphoma],” Dr. Yang and his colleagues wrote. “Therefore, we hypothesized that lymphopenia may be integrated with existing FLIPI to better stratify long-term survival outcomes and predict for transformation.”
The researchers tested this theory in 736 follicular lymphoma patients who were followed for a median of 72 months (range, 2-211 months). The 5-year OS in this cohort was 81.3%, the 10-year OS was 67.3%, and 18% of patients experienced transformation to high-grade lymphoma.
The researchers defined absolute lymphopenia as less than 1.0 × 109 lymphocytes per liter. In multivariate analyses, lymphopenia was an independent predictor of OS (hazard ratio, 1.74; P less than .01) and transformation (odds ratio, 2.1; P less than .01).
To incorporate lymphopenia into the FLIPI, the researchers created a model in which 1 point was given for each of the standard FLIPI components (age, Ann Arbor stage, number of nodal areas, lactate dehydrogenase, and hemoglobin level), and one point was given for the presence of lymphopenia. Patients in the low-risk FLIPI-L category had 0-1 points, those in the intermediate-risk category had 2-3 points, and patients in the high-risk FLIPI-L category had 4-6 points.
Using the original FLIPI, the 5-year OS was 91% in the low-risk group (0-1), 82.7% in the intermediate-risk group (2), and 66% in the high-risk group (3-5). The 10-year OS was 80.4%, 66%, and 45.8%, respectively.
Using the FLIPI-L, the 5-year OS was 94.5% in the low-risk group (0-1), 89% in the intermediate-risk group (2-3), and 61% in the high-risk group (4-6). The 10-year OS was 83.9%, 68.5%, and 34.5%, respectively.
In a univariate Cox regression analysis of OS, each point increase in FLIPI-L score was associated with a significant increase in hazard ratio. For example, the hazard ratio was 3.4 for patients with a FLIPI-L score of 1 and 30.9 for those with a FLIPI-L score of 6 (P less than .02 for all FLIPI-L scores). Conversely, increases in hazard ratio were not significant with the original FLIPI (P greater than .05 for all FLIPI scores).
The FLIPI-L was prognostic for OS in different treatment groups. In patients who received rituximab alone, radiation alone, or rituximab plus chemotherapy, the scoring system differentiated low-, intermediate-, and high-risk groups (P less than .04). In patients under observation, the FLIPI-L distinguished low/intermediate-risk and high-risk groups (P less than .01).
For patients who progressed within 24 months, the FLIPI-L was more predictive of progression-free survival (P = .05) than was the original FLIPI (P = .11).
Increasing FLIPI-L was an independent predictor of transformation, both when assessed as a continuous variable (P less than .01) and stepwise for FLIPI-L 3-5 (P = .004-.01). The original FLIPI, on the other hand, was not an independent predictor of transformation.
“Our analysis of a lymphopenia cutoff as an addition to the original FLIPI is simple yet improves risk stratification to differentiate between prognostic groups and, importantly, to predict transformation,” Dr. Yang and his colleagues wrote.
The authors reported having no conflicts of interest.
SOURCE: Yang G et al. Blood Cancer J. 2020 Jan 2;9(12):104. doi: 10.1038/s41408-019-0269-6.