A Proposed Prognostic Model For Overall Survival In The Oldest Old (>80 Years Old) Follicular Lymphoma Patients
Authors: Nabhan Chadi , Byrtek Michelle , Dawson Keith L , Zhou Xiaolei , Link Brian K , Friedberg Jonathan W. , Zelenetz Andrew D. , Cerhan James R , Flowers Christopher R. 
Published: October 2019

Abstract

Background
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.

Patients/Methods
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.

Results
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).

Conclusions
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.

Disclosures:
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.