Real-World Patterns of Care for Patients with Follicular Lymphoma Treated with Lenalidomide and Rituximab (R²) in the US Medicare Population

Introduction: Follicular lymphoma (FL) is the most common indolent lymphoma and the second most common subtype of non-Hodgkin lymphoma (NHL). While rituximab-based immunochemotherapy remains a standard in front-line and relapsed FL settings, novel therapies hold the potential for chemotherapy-free treatment and may offer particular clinical benefit in the subgroup of patients with early relapse following immunochemotherapy. Rituximab with lenalidomide (R²) represents one such chemotherapy-free regimen currently in late-stage clinical trials for indolent lymphoma. While we await final reports from these ongoing trials, little is known about the current use of R² in the routine care of patients with FL.

M ethods: Our population-based cohort study utilized 100% Medicare claims data from January 2009 through December 2014. We selected a population of patients with FL (ICD-9: 202.0x) with at least one claim for rituximab during the identification period (January 1, 2010 through October 31, 2014). We then identified the subgroup of patients who received R² by requiring claims for at least two consecutive cycles of lenalidomide and rituximab. The first prescription date for lenalidomide was defined as the index date. Patients were required to have continuous medical and pharmacy benefits for ≥ 12 months pre-index date (the baseline period), and ≥ 2 months post-index date (the follow-up period). Treatment discontinuation was defined as a gap in therapy of > 60 days. Patients initiating R² within 90 days of a prior treatment were considered refractory to previous therapy. Patient demographics, clinical characteristics, and previous treatment regimens were recorded throughout the pre-index period. Patients receiving R² were followed until the end of data availability.

Results: Of 18,199 patients with FL receiving rituximab-based therapy during our study period, 226 (1.2%) were identified as receiving R². The median age at the time of receiving R² was 75 years (interquartile range [IQR] = 9 years); patients were mostly male (56.2%) and white (89.8%). Comorbid conditions at the initiation of R² therapy were common, with a mean Charlson comorbidity index score of 5.1. Medical claims related to anemia (65.5%), chronic obstructive pulmonary disease (36.7%), and kidney dysfunction (30.5%) were the most prevalent comorbid conditions. The median time from the first identifiable FL claim until R² initiation was 589 days (IQR = 895 days). Almost all patients (n = 224) showed evidence of previous FL-related treatment, with 39% showing evidence of at least two prior lines of treatment during the study period before initiating R² therapy. A significant proportion of patients were refractory to their previous therapy (57.5%), and of those patients 35.3% were receiving R-chemotherapy, 26.2% were receiving rituximab monotherapy, and the remaining 38.5% were receiving other chemotherapy agent or regimens. The most frequent treatment regimens received in the pre-R² period were rituximab monotherapy (42.5%), rituximab + bendamustine (38.9%), R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone [24.4%]), and rituximab + cyclophosphamide (20.4%). Additionally, 26.1% of patients had prior radiotherapy use. The median treatment gap between previous FL therapy and R² was 124 days (IQR = 293 days). The median duration of R² therapy was 100 days (IQR = 99 days).

Conclusions: In our large US population-based study of older patients with FL receiving therapy between 2009 and 2014, R² therapy was used infrequently compared with rituximab monotherapy and standard immunochemotherapy. R² was nearly exclusively administered in the relapsed setting, with almost half of patients receiving R² immediately being refractory to other rituximab-based treatments. With claims through the end of 2014, our study does not account for the impact of other recently approved novel FL therapies. Overall, R² therapy has historically been limited to the relapsed/refractory FL setting and future observational studies will be important to assess whether upcoming R² trial results impact FL treatment and outcomes in the real-world setting.