Comparison of Survival and Costs of Rituximab-Based Chemotherapy for Initial Therapy of Follicular Lymphoma in Elderly Patients
Authors: Shah Gunjan L. , Winn Aaron , Lin Pei-Jung , Kumar Anita J , Parsons Susan K 
Published: October 2019

Abstract
Introduction: The addition of rituximab to combination chemotherapy has been shown to be cost-effective in the care of lymphoma patients. However, there is little literature evaluating the differences in survival and cost of care between first line rituximab-based combinations. We aimed to focus on older patients with follicular lymphoma (FL) as the standard of care is evolving for these patients.
Methods: We identifiedstage II-IV grade 3 FL patients over the age of 66 diagnosed between 2001-2010 who received chemotherapy within 6 months of diagnosis using ICD-O codes and data from the Surveillance, Epidemiology, and End Results (SEER) Program. We then collected the healthcare costs from linked with Medicare claims through 2014. Comorbidity was calculated based on the modified Charlson Comorbidity Index (CCI). We estimated the costs using a phase of care approach. For patients surviving over 2 years, we estimated three time periods of monthly costs: first year after diagnosis, the time between the first and last years with the disease, and the final year of life. For those that live under 2 years after diagnosis, consistent with the literature, we estimated the total costs for their entire trajectory. For censored patients, we simulated their life expectancy and lifetime costs until death. To estimate the life time costs under each treatment regime, we simulated 10,000 hypothetical patients and their life-expectancy and assigned their costs based on the length of their lives.
Results: Of the 1095 FL patients meeting criteria, 485 (44%) received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), 393 (36%) received rituximab and a different combination chemotherapy (R-chemo), and 217 (20%) received rituximab alone (R). R-CHOP patients were younger than R-chemo or R-alone treated patients [median age 73 (SD 5.5), 76 (6.4), 79 (6.8), respectively], with 41%, 54%, and 71% over age 75, respectively (p<0.001). R-CHOP treated patients more frequently had no comorbidities (R-CHOP 55%, R-Chemo 45%, R 51%, p=<0.001) and were married (R-CHOP 66%, R-Chemo 54%, R 56%, p=0.01). Higher stage was more commonly treated with R-CHOP or R-Chemo (stage IV R-CHOP 39%, R-Chemo 35%, R 24%, p=0.003), as expected. Patients treated in large metropolitan areas were more likely to receive more intense therapy (R-CHOP 55%, R-Chemo 45%,R 51%), while in less urban areas all three regimens were used with similar frequency (R-CHOP 11%, R-Chemo 9%, R 10%) (p=0.03). Census tract poverty level was similar between all 3 groups. The predominant therapy changed over time with R-Chemo becoming more common in recent years (2010 R-CHOP 7%, R-Chemo 14%, R 11%, p=0.02). Median overall survival from diagnosis was 6 years after first line R-CHOP, 4.8 years after R-Chemo, and 4.5 years after R (p<0.001, Figure 1).
Total mean costs from diagnosis until death were $130,300 in R-CHOP treated patients, $114,800 in R-Chemo, and $108,000 in R alone. For patients who lived less than 2 years, the mean monthly costs were similar between R-Chemo [$7,700 (5th-95th percentile 6,800-8,600)] and R [$7,900 (6,900-8,900)], but higher with R-CHOP [$9,100 (8,000-10,200)]. For patients living longer than 2 years, the mean monthly costs in the first year after diagnosis were similar for R-CHOP [$1,600 (1,500-1,700)] and R-Chemo [$1,600 (1,500-1,800)], but lower for R [$1,300 (1,200-1,400)]. Similarly in the last year of life, the median monthly cost for R-CHOP treated patients was $5,600 (5,200-6,100), R-Chemo $5,500 (5,000-6,000), and R [$4,800 (4,300-5,200)].
Conclusions: In this first analysis of differences between rituximab based combinations in older adults with FL, we find that the addition of an anthracycline (R-CHOP) increased survival, but with similar cost. In addition, given the dramatic differences in cost between the first year after diagnosis and the last year of life, the major driver of expenditure is likely related to subsequent lines of care. Our future results will include adjusted analyses, additional FL populations, and evaluation of therapy after 1st relapse.
Figure 1 Overall SurvivalByRituximab Containing Induction Regimens in FL Figure 1. Overall SurvivalByRituximab Containing Induction Regimens in FL

Disclosures
No relevant conflicts of interest to declare.