LAUSR

s from OT01 to OT06 can be found in the pertinent section, after the PUBLICATION section. “FOCUS ON...” SESSION: LYMPHOMA IN THE ELDERLY 87 HIGHER MUTATIONAL BURDEN BUT DOES NOT IMPACT TREATMENT EFFICACY IN FOLLICULAR LYMPHOMA S. Alig* | V. Jurinovic | M. Dreyling | A. Pastore | R. Kridel | R. Gascoyne | W. Hiddemann | M. Unterhalt | E. Hoster | O. Weigert Medical Department III, Ludwig‐Maximilians‐University, Munich, Germany; Medical Department III & Institute for Medical Informatics, Biometry and Epidemiology, Ludwig‐Maximilians‐University, Munich, Germany; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, USA; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre – University Health Network, Toronto, Canada; Centre for Lymphoid Cancer & Department of Pathology and Laboratory Medicine, BC Cancer Agency, Vancouver, Canada Introduction: Higher age is associated with shorter overall survival (OS) in patients (pts) with follicular lymphoma (FL), and age > 60 years is a component of the FL International Prognostic Index (FLIPI). However, it is unclear whether higher age directly impacts disease biology or treatment efficacy in FL. Methods: We analyzed 755 pts from the GLSG2000 trial who received R‐CHOP for symptomatic, advanced stage FL. Pts who received consolidative autologous stem cell transplantation were censored at time of transplant. Progression of disease (POD) included progressive, relapsed or refractory disease (40‐50 yrs, 261 (35%) >50‐60 yrs, 208 (28%) >60‐70 yrs, and 58 (8%) >70 yrs. 5‐ year OS rates were 97%, 91%, 90%, 85%, and 53% (Figure A); 5‐ year FFS rates were 82%, 62%, 63%, 55%, and 42% (Figure B), respectively. We used the cohort >50‐60 yrs as a reference. Older pts had inferior OS (>60‐70 yrs: HR 1.90, 95%‐CI [1.15; 3.13], p = 0.012; >70 yrs: HR 7.31, 95%‐CI [4.25; 12.59], p < 0.0001). Significantly inferior FFS was only seen in pts >70 yrs (HR 2.17, 95%‐CI [1.45; 3.25], p = 0.00016). Competing risk analysis revealed that inferior FFS of pts >70 yrs did not result from increased POD (HR 1.20, 95%‐CI [0.75; 1.91], p = 0.45), but from higher incidence of death without prior POD (HR 24.81, 95%‐CI [5.38; 114.44], p < 0.0001; Figure C).Sequencing data of diagnostic FL biopsies from 258 pts showed that the number of gene mutations increased with age (RR 1.14/decade, 95%‐CI [1.09; 1.20], p < 0.0001). This increase was however caused by silent mutations and mutations predicted to have low functional impact (each p < 0.0001), whereas disruptive mutations or mutations predicted to have high functional impact did not significantly increase with age (p = 0.27 and p = 0.16, respectively). Similarly, the number of mutated genes increased with age (RR 1.12/decade, 95%‐CI [1.07; 1.18], p < 0.0001), but the fraction of significantly mutated genes (by MutSigCV) decreased from 89% (range 40‐100%) in young adults (18‐40 yrs) to 74% (range 0‐ 100%, p = 0.01) in the oldest cohort (>70 yrs). No single gene mutation was found to be associated with older age after correction for multiple testing. Conclusions: Our data suggest that older age does not directly impact disease biology and treatment efficacy in FL, and should not be used to guide treatment decisions.