Treatment Patterns and Real World Outcomes with Clinical Trials for Patients with Follicular Lymphoma across Lines of Therapy

Introduction

Follicular Lymphoma (FL) is a biologically heterogenous disease, without a single established standard of care (SOC) treatment for any line of therapy. While overall survival (OS) remains favorable, clinical trials (CT) are appropriate at first-line (1L) and in each subsequent line of therapy since cure with SOC is rare. Moreover, high risk groups at each line include patients who have progression of disease in 24 months (POD24), and/or experience transformation to large cell lymphoma. However, limited real world evidence exists regarding the outcomes associated with SOC and CTs across lines of treatment. This study aims to evaluate FL and high risk FL patients receiving SOC vs. CT.

Methods

This retrospective cohort study utilized data from patients receiving care at MD Anderson Cancer Center who received treatment between 1989-2020 and received ≥3 lines of treatment. Clinical data and patient outcomes were abstracted from the database and electronic medical records when needed following a standard protocol. Outcomes of interest were progression free survival (PFS), OS, and response rates. Responses were assessed by Lugano 2014 criteria and/or clinician assessment. Time to event variables were estimated using Kaplan-Meier methods and compared using the Log-rank test.

Results

183 patients were included in this study. In the 1L setting 30 (17%) patients were treated on CT, in the second line (2L) 39 (23%) patients were treated on CT, and in the third line (3L), 39 (23%) patients were treated on CT. Common SOC therapies included rituximab (R; 1L 5.8%; 2L 25%, 3L 12.3%), R-CHOP (1L 32.9%; 2L 8.9%, 3L 7%), bendamustine-R (1L 13.9%; 2L 10.1%, 3L 14%), and lenalidomide-R (3L 5.8%). Of patients with available response data, there was no significant difference in complete response rate (CRR) in patients receiving SOC compared to CT in each line. In the 1L setting CRR was 48% in SOC vs 60% in CT. For 2L CRR was 37% in SOC vs 33% in CT, and for 3L CRR was 51% in SOC vs 49% in CT. There was no significant difference in median PFS (mPFS) in the SOC group vs. CT group in both 1L and 3L. mPFS was 22.6 months in SOC vs. 24.7 in CT in 1L, and 22.1 months in SOC vs 16.5 months in CT in 3L. There was a significantly longer PFS in the SOC group compared to CT group in the 2L setting, with mPFS of 12 months in SOC vs. 8.3 months in CT (p=.001). OS was not significantly different between the SOC and CT groups in all lines of treatment. In 1L SOC vs. CT mOS was 250 months vs. not reached (NR) respectively, in 2L 153 months vs NR respectively, and in 3L 149 months vs. 148 months respectively. In 1L, there were 10 transformations (7%) in SOC and 1 (3.3%) in CT. In 2L 14 (10.9%) transformations occurred in SOC vs. 4 (10.3%) in CT, and in 3L 10 (7.6%) transformations occurred in SOC vs. 2 (5.1%) in CT. 87 patients were POD24 after 1L treatment. Of these patients 74 (57%) received SOC and 13 (33%) received CT. Of the POD24 population with available response data (N=83), there was no significant difference in CRR, PFS, or OS in the SOC group vs. CT group. CRR to 1L therapy was 31% in SOC vs. 33% in CT. mPFS was 9.35 months in SOC and 7.47 in CT and mOS was NR in both groups. 14 patients transformed in the POD24 population, 11 received SOC, 3 received CT.

Conclusion

In patients receiving treatment for FL at a single center, there was no difference in CRR and mOS when comparing patients receiving treatment with SOC vs. CT across all lines of treatment. Similar to what other studies have shown, mPFS and mOS decline with each subsequent line of therapy. In POD24 patients there was no difference in CRR, mPFS, and mOS when comparing patients who received treatment with SOC vs. CT in the 1L. These data suggest that patients who utilize CT can have similar response rates and survival to patients who received SOC, providing real world evidence that CTs do not negatively impact outcomes, and therefore can be considered across all lines of therapy.