Challenges for quality and utilization of real-world data for diffuse large B-cell lymphoma in REALYSA, a LYSA cohort

Abstract

Real-world data (RWD) are essential to complement clinical trial (CT) data, but major challenges remain, such as data quality. REal world dAta in LYmphoma and Survival in Adults (REALYSA) is a prospective noninterventional multicentric cohort started in 2018 that included patients newly diagnosed with lymphoma in France. Herein is a proof-of-concept analysis on patients with first-line diffuse large B-cell lymphoma (DLBCL) to (1) evaluate the capacity of the cohort to provide robust data through a multistep validation process; (2) assess the consistency of the results; and (3) conduct an exploratory transportability assessment of 2 recent phase 3 CTs (POLARIX and SENIOR). The analysis population comprised 645 patients with DLBCL included before 31 March 2021 who received immunochemotherapy and for whom 3589 queries were generated, resulting in high data completeness (<4% missing data). Median age was 66 years, with mostly advanced-stage disease and high international prognostic index (IPI) score. Treatments were mostly rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP 75%) and reduced dose R-CHOP (13%). Estimated 1-year event-free survival (EFS) and overall survival rates were 77.9% and 90.0%, respectively (median follow-up, 9.9 months). Regarding transportability, when applying the CT's main inclusion criteria (age, performance status, and IPI), outcomes seemed comparable between patients in REALYSA and standard arms of POLARIX (1-year progression-free survival 79.8% vs 79.8%) and SENIOR (1-year EFS, 64.5% vs 60.0%). With its rigorous data validation process, REALYSA provides high-quality RWD, thus constituting a platform for numerous scientific purposes. The REALYSA study was registered at www.clinicaltrials.gov as #NCT03869619.

Graphical abstract

Figure 1.

Automated patient profile. The patient profile is divided into 4 main parts. In the upper left part, the patient and tumor characteristics at inclusion are described. In the upper right part, the involvements (nodal and extra-nodal) at diagnosis are reported. Red circles are automatically located on the man/woman (depending on patient’s sex) to represent nodal involvements. Nodal involvements reported in the “other” section of the eCRF appear in the red box in the upper right part. Extra-nodal involvements are detailed in the blue box in the lower right part. In the graph on the left, the longitudinal information per line(s) of treatment is indicated, with a gray horizontal bar per line of treatment (the treatment cycles are symbolized by black vertical lines), with the evaluations of the responses (circle above the line with color code according to the response: green for complete response, light green for partial response, orange for stable disease, and red for progressive disease) and the events (progression [inverted red triangle], adverse events [red cross, not present for this patient], and death [crossed out circle]). Note: all colors and symbols are not depicted in this patient profile example. Finally, in the lower right part, follow-up information is reported.

Figure 2.

Study flowchart.

Figure 3.

Prognostic value of IPI and aaIPI on event-free survival. EFS according to IPI (A) and aaIPI (B). CL, confidence limit.