The prognostic value of progressing within 24 months of frontline chemoimmunotherapy (POD24) in relapsed/refractory (R/R) follicular lymphoma (FL)—a SCHOLAR‐5 analysis

Abstract

Introduction: FL has a heterogeneous prognosis with multiple risk factors associated with shorter overall survival (OS). Whilst patients whose FL progresses within 24 months (POD24) after frontline chemo-immunotherapy (CIT) have poor OS (50% at 5 year vs. 90% non-POD24, HR of 7.17, 95% CI: 4.83–10.65, Casulo et al. [J Clin. Oncol., 33(23):2516–2522 (2015)]). The role of POD24 as a prognostic factor in later lines is less clear. We sought to investigate whether POD24 remains a key prognostic factor in R/R FL patients initiating ≥3rd line of therapy (LoT). Methods: The electronic medical record (EMR) component of the SCHOLAR-5 cohort of R/R FL patients served as the evidence base for this analysis. POD24 was defined as relapse within 24 months of initiating frontline CIT (Patients who relapsed within 24 months of initiating rituximab monotherapy or another class of frontline therapy were non-POD24). Analyses included LoT, gender and stem-cell transplant in current LoT as covariates. OS was analyzed using Cox regression with time-dependent variables and a single outcome for each patient. Progression-free survival (PFS) was analyzed using repeated measures Cox regression. Overall response rate (ORR) and complete response (CR) were analyzed using repeated measures logistic regression producing an odds ratio. Additional sensitivity analyses explored alternate definitions of POD24 and different model specifications. Results: A total of 123 patients met the inclusion criteria, with 34 (27.6%) defined as POD24. Patient characteristics at initiation of frontline therapy were comparable between POD24 and non-POD24 groups. At first eligible LoT (≥3rd), POD24 patients were notable for a significantly shorter time since initial diagnosis, and a higher probability for being refractory to their last line of therapy. POD24 was associated with shorter OS OS (Figure 1) with a hazard ratio (HR) of 1.92 (95% confidence interval [CI]: 1.16, 3.16). Although all estimates for other clinical outcomes were in the same direction they were not statistically significantly s (PFS HR: 1.27; 95% CI: 0.96, 1.69, ORR odds ratio: 1.44; 95% CI: 0.80, 2.97, CR odds ratio: 1.45; 95% CI% 0.65, 3.30). Patients refractory to their last LoT were at increased risk of progression (HR: 1.48; 95% CI: 1.05, 2.09), but this was not associated with OS. The research was funded by: Kite, A Gilead Company Keywords: Cellular therapies, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. A. R. Patel Employment or leadership position: Gilead/Kite Stock ownership: Gilead/Kite E. H. Limbrick-Oldfield Employment or leadership position: RainCity Analytics S. Kanters Employment or leadership position: RainCity Analytics Research funding: RainCity Analytics M. D. Ray Employment or leadership position: Gilead/Kite Stock ownership: Gilead/Kite T. Best Employment or leadership position: Gilead/Kite Stock ownership: Gilead/Kite P. Ghione Consultant or advisory role: AstraZeneca, Kyowa Hakko Kirin, Secura Bio Research funding: Gilead/Kite S. S. Neelapu Consultant or advisory role: Gilead/Kite, Merck, BMS, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Adicet BioLegend Biotech, Calibr, Unum Therapeutics, Bluebird Bio, Medscape, Aptitude Health, Bio Ascend Honoraria: Gilead/Kite, Merck, BMS, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Adicet Bio, Legend Biotech, Calibr, Unum Therapeutics, Bluebird Bio, Medscape, Bio Ascend Research funding: Gilead/Kite, Merck, BMS, Celgene, Allogene Therapeutics, Precision Biosciences, Adicet Bio, Unum Therapeutics, Aptitude Health, Poseida, Cellectis, Karus Therapeutics, Acerta Other remuneration: Gilead/Kite, Merck, BMS, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics, Takeda Pharmaceuticals J. G. Gribben Honoraria: Janssen, AbbVie, AstraZeneca, Amgen, BMS, Gilead/Kite, Novartis Research funding: Celgene, AstraZeneca, BMS Other remuneration: Janssen, AbbVie, Roche/Genentech S. Beygi Employment or leadership position: Gilead/Kite Research funding: Gilead/Kite