Survival Outcomes after First-Line Therapy in Follicular Lymphoma Patients Treated with Bendamustine and Rituximab Vs Other Rituximab Combinations in the United States

Background: Follicular lymphoma (FL) is a heterogeneous disease, and clinical presentation is highly variable. The Follicular Lymphoma International Prognostic Index (FLIPI-2) identifies prognostic factors at diagnosis, but does not predict in whom and when to initiate first-line therapy (1LT) (Federico 2009). Recommended therapies for 1LT vary by stage, symptomatology, and tumor burden, but include monotherapy with rituximab (R) or in combination with other chemotherapies. Survival of FL patients in the R era has greatly improved, but few studies have evaluated survival outcomes in patients seen in routine clinical care. This study aimed to evaluate survival outcomes in a United States (US) population of newly diagnosed FL patients seen in routine clinical care.

Methods: A retrospective study was conducted in which the presence of ≥1 inpatient record or ≥2 outpatient records with FL diagnosis codes were used to identified newly diagnosed FL patients from Humedica, a large US electronic medical record database, between 01/01/08 and 07/31/15. The study index date was the first FL record. Patients who subsequently initiated 1LT with bendamustine+R or other R-based combinations were followed from the date of treatment initiation until death, loss to follow-up, or end of study (09/30/15) for the evaluation of the survival outcomes. Median progression-free survival (PFS) (defined as initiation of second-line therapy, evidence of supportive care >30 days after the end of a line of therapy, or death), median overall survival (OS), and PFS and OS rates at 2 years following initiation of 1LT were evaluated using Kaplan-Meier analyses. Cox proportional hazard models were used to further assess the impact of bendamustine+R and other R-based combinations on OS and PFS at 2 years.

Results: 1,346 newly diagnosed FL patients who initiated 1LT met the patient selection criteria; of these, 362 and 417 received bendamustine+R and other R-based combinations, respectively. The majority of the other R-based combinations were R-CHOP (48.7%) and R-CVP (25.4%). The mean age (bendamustine+R, 65.3 [SD: 11.5] and other R-based combinations, 65.0 [SD: 11.6]) and proportion of males (bendamustine+R, 48.9% and R-based combinations, 48.0%) were similar between the two treatment groups. At baseline, 19.3% of patients treated with bendamustine+R and 15.3% of patients treated with other R-based combinations had a Charlson Comorbidity Index of ≥2. Unadjusted Kaplan-Meier analysis revealed that for patients treated with bendamustine+R and R-based combinations, 2-year OS rates were 90.2% and 86.2% (P=0.0916), respectively, and 2-year PFS rates were 76.7% and 56.0% (P <0.0001), respectively. Median OS was not reached in both treatment groups, and median PFS was not reached in the bendamustine+R and was 36.4 months (95% CI: 24.3, 47.3) for patients treated with other R-based combinations. In the adjusted, no significant difference was observed between the two treatment groups for the 2-year OS; however, the bendamustine+R when compared to the other R-based combinations had a lower hazard for progression at 2 years (0.42; 95% CI: 0.31, 0.58).

Conclusion: In routine clinical practice, patients treated with bendamustine+R in 1LT had significantly better 2-year PFS than patients treated with other R-based combination therapy, while OS was similar between the groups. These results are similar to that of the clinical trial comparing bendamustine plus rituximab and R-CHOP, where PFS was found to be significantly better with bendamustine plus rituximab and OS was similar (Rummel 2009).