Treatment Patterns and Health/Economic Outcomes in Relapsed/Refractory Follicular Lymphoma: A Real-World Study

Abstract

Background:Indolent non-Hodgkin lymphoma (iNHL) is a hematologic malignancy characterized by slow progression. Follicular lymphoma (FL) is the most common subtype of iNHL. Although responses to first-line therapy can be high, patients with FL often relapse repeatedly. There are no guidelines for the treatment of relapsed/refractory (R/R) FL and the economic impact in Canada is unknown. The objective of this study was to evaluate treatment patterns, as well as health care resource utilization and costs, associated with the management of R/R FL in Canada.Methods:A retrospective medical chart review was conducted in 3 Canadian Oncology centers. Eligible patients were ≥18 years, diagnosed with FL, had received prior treatment with ≥2 systemic therapies, and were refractory to rituximab and an alkylating agent (administered together or in succession). Date of inclusion in this study was defined as the date of FL diagnosis. Index date was defined as the date at which the patient met all eligibility criteria. End of study was defined as death, loss to follow-up, or March 31, 2015, whichever came first. To ensure a sufficient follow-up period, index date had to predate January 1, 2014. Data collected included patient, disease, and treatment characteristics, as well as health care resource utilization. Treatments and outcomes were collected from date of inclusion until end of study. Health care resource utilization was collected from index date to end of the study. Canadian unit costs were obtained from the literature and government publications.Results:A total of 24 patients with FL met the study eligibility criteria at these centers. FL diagnosis was established between April 1990 and January 2012 and index date was reached between May 2001 and October 2013. The median age at index date was 64 years (range, 47-82) and 62.5% were female. Most patients (83.4%) had a stage III or IV FL at index date. The median time from FL diagnosis to index date was 6.0 years (0.8-22.3) and the median time from index date to end of study was 2.6 years (0.1-13.9). The median number of treatment lines was 2 (2-4) prior to index date and 3.5 (2.0-5.0) through the overall study period. A total of 22 different treatment regimens were identified in this study, and each patient showed a unique treatment pattern. Following index date, 66.7% of treatments continued to consist of rituximab- and/or alkylating agent-based therapies, despite prior progression on, and refractoriness to, these regimens. Hematopoietic stem cell transplant was more common after the index date. Overall, median time to relapsed/refractory diagnosis (TRRD) was 18.2 months (1.2-107.2) before index date and 9.6 months (0.7-51.5) after index date. For patients who received a non-rituximab-containing regimen in first-line and a rituximab-containing regimen in second-line, median TTRD was 52.0 months (12.6-76.2); for patients who received a rituximab-containing regimen in first- and second-line, median TTRD was 4.0 months (1.3-5.5). In general, with each line of treatment, the proportion of different treatment regimens administered increased, whereas the number of patients receiving therapy decreased. Furthermore, median TTRD, treatment duration, and time between treatments generally decreased with each subsequent line of treatment. Median overall survival was not reached. Mean monthly cost per patient was C$4,793 including hospitalizations (56%, average of 2.6 days per month), treatments (24%), medical procedures (19%) and outpatient medical visits (1%).Conclusions:This study characterizes health and economic outcomes in a highly specific FL patient population refractory to rituximab and an alkylating agent. The results demonstrate that treatment patterns were heterogeneous and patients became less responsive to available therapies over time. Furthermore, there was no consistent standard of care for these R/R FL patients, with many continuing to receive rituximab and/or alkylating agents despite prior relapse on, and refractoriness to, these regimens. These results suggest that the management of patients with R/R FL becomes increasingly challenging throughout the course of the disease, and is associated with considerable costs driven mainly by hospitalizations. Thus, new effective treatment options are clearly warranted for R/R FL patients.Source of supportThis study was supported by Gilead Sciences Canada Inc. Disclosuresvan der Jagt:Lundbeck, Teva: Consultancy; Teva: Research Funding. Fleury:Novartis Pharmaceuticals Corporation: Consultancy; Merck: Consultancy; Janssen: Consultancy; Roche: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy; Amgen: Consultancy; Lundbeck: Consultancy. Wagner:Gilead Sciences Canada: Employment, Equity Ownership. Toltl:Gilead Sciences Canada: Employment, Equity Ownership. Lachaine:Gilead Sciences Canada: Research Funding.