A Proposed Prognostic Model For Overall Survival In The Oldest Old (>80 Years Old) Follicular Lymphoma Patients

Disease characteristics, treatment patterns, and outcomes of follicular lymphoma (FL) patients (pts) aged >80 years (yrs) are infrequently reported. Further, the original Follicular Lymphoma International Prognostic Index (FLIPI) has not been formally studied in pts aged >80 yrs. Also, whether FLIPI is associated with overall survival (OS) in pts aged >80 yrs is unknown.

We used the National LymphoCare Study—a Genentech-sponsored, prospective, multicenter registry of FL pts across the United States without study-specific treatment—to comprehensively analyze FL pts aged >80 yrs. Using Pearson chi-squared tests, associations of age groups with disease characteristics and overall response rate (ORR) were examined. Median progression-free survival (PFS) and OS by treatment regimen were estimated using the Kaplan-Meier method. Cox proportional hazards regression that were adjusted for baseline disease factors were used to assess treatment differences in PFS, lymphoma-related mortality (LRM, which includes both disease and treatment-related deaths), and OS, as well as the significance of age by treatment interactions. FLIPI and a prognostic model that was constructed based on the findings were used to predict outcomes.

Of 2649 evaluable pts, 209 (8%) were aged >80 yrs. Compared with pts aged ≤60, pts aged >80 yrs were more likely to be Caucasian, to have worse performance status, to have lower hemoglobin (Hgb) value (<12 g/dL), to have less advanced stage, and were less likely to be treated at academic institutions. When treated, pts aged >80 yrs had lower ORR compared with younger pts and were less likely to receive rituximab + chemotherapy (P <.001) or anthracyclines (P <.001). Use of maintenance rituximab was not significantly different between pt groups when rituximab induction was given (61% for pts aged ≤60, 38% for pts aged >80, P=.11), but it was more frequent in pts aged >80 yrs when rituximab + chemotherapy induction was administered (44% for pts aged ≤60, 59% for pts aged >80, P=.04). After adjusting for maintenance use, sex, and baseline factors, age significantly differentiated PFS impact of observation, rituximab monotherapy, and rituximab + chemotherapy (P=.01). No treatment regimen provided superior PFS or OS in pts aged >80 yrs. With a median follow-up of 6.5 yrs for all pts (4.3 yrs for pts aged >80 yrs), 5-year OS was 59% and 92%for patients aged >80 and ≤60 yrs, respectively. OS in pts aged >80 yrs varied based on FLIPI score (log-rank test, P=.01; Figure 1). Interestingly, the percentage of deaths that were disease-related was 40% in pts aged >80 yrs, which was comparable to the percentage in pts aged ≤60 yrs of 48%. Cox modeling showed that lower Hgb, B symptoms, and male sex predicted worse OS (P<.01) but not PFS in pts aged >80 yrs. Recognizing that males have inferior OS compared with females in the general population, we constructed a prognostic model composed only of B symptoms and Hgb level <12 (low risk=no factors; high risk=1 or more factors; P<.0001; Figure 2). FLIPI and the proposed prognostic model significantly differentiated both OS and LRM (Table 1).

View largeDownload slide

View largeDownload slide

Close modal

View largeDownload slide

View largeDownload slide

Close modal

In the largest, prospectively published study of FL pts aged >80 yrs, OS, PFS, ORR, and treatment selection varied compared with younger pts. Surprisingly, the proportion of deaths attributed to lymphoma in these older FL pts was 40%. FLIPI was associated with outcome in pts aged >80 yrs and so was a proposed prognostic model comprising lower Hgb and B symptoms. Independent validation of this model is required, and additional prospective studies that are designed for the oldest old are warranted.

Nabhan:Genentech Inc.: Advisory Board Other, Honoraria. Byrtek:Genentech, a member of the Roche group: Employment, Equity Ownership; Roche: Equity Ownership, stock options, stock options Other. Dawson:Genentech: Employment; Roche: Equity Ownership. Link:Genentech: Consultancy; Millenium: Consultancy; Pharmacyclics: Consultancy; Spectrum: Consultancy; Genentech: Research Funding; Millenium: Research Funding; Pharacyclics: Research Funding. Zelenetz:GSK: Consultancy; Celgene: Consultancy; Cephalon: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; Sanofi-Aventis: Consultancy; Genentech: Research Funding; GSK: Research Funding; Roche: Research Funding; Cancer Genetics: Scientific Advisor Other. Cerhan:Genentech: Scientific Advisory Board of the National LymphoCare Study Other. Flowers:Abbott, Celgene, Millennium/Takeda, Sanofi, Spectrum, Janssen: Research Funding; Celgene, Genentech Bio-oncology: Consultancy.