The REALYSA cohort, a real-world data source including patients in France newly diagnosed with lymphoma, showed baseline characteristics, treatments, and outcomes for patients with diffuse large B-cell lymphoma (DLBCL) on firstline therapy consistent with those from two recent clinical trials. This is according to a proof-of-concept study, published in Blood Advances, which also found that the database had minimal missing data on key variables.1
REALYSA cannot ensure coverage of all patients with DLBCL in France, but the results were consistent with current treatment guidelines and reflect “the implementation of clinical trial results into routine care,” said corresponding author Hervé Ghesquières, MD, PhD, of Lyon Sud Hospital in Pierre-Bénite, France.
Real-world data are needed to complement clinical trials, with limited participation or criteria that may exclude several patients newly diagnosed with DLBCL. In 2018, the Lymphoma Study Association (LYSA) launched REALYSA, an observational multicentric prospective cohort in France, to evaluate the real-world prognosis of the seven most common lymphoma subtypes. Specifically, patients 18 years or older who were diagnosed with lymphoma in the previous six months and before treatment initiation were prospectively recruited in one of 35 hematology centers. Treatment was according to physician’s choice with no compulsory visits.
In this proof-of-concept analysis of the firstline treatment of patients in the cohort with DLBCL, the researchers evaluated the capacity of the cohort to provide robust data; assessed whether the cohort’s characteristics, clinical practices, and estimated effectiveness were consistent with what is expected in real life; and assessed the transportability of the cohort to those in the prospective phase III POLARIX and SENIOR trials, which evaluated newer firstline therapeutic agents in patients with DLBCL.2,3
The analysis included 645 patients with DLBCL who had received immunochemotherapy and were recruited into REALYSA before March 31, 2021.1 A total of 3,589 queries were generated, resulting in less than 4% missing data. The median age of the patients was 66 years (range = 19-98). Fifty-three percent of the patients were male, 73% had advanced-stage disease (Ann-Arbor stage III/IV), and 76% had a high international prognostic index (IPI) score of 2-5. Firstline treatments were mostly R-CHOP (rituximab, doxorubicin, cyclophosphamide, vincristine, prednisone) and reduced-dose R-CHOP, or high-dose anthracycline-based regimens, at 75%, 13%, and 10%, respectively. Only 2% of patients received a non-anthracycline-based regimen. The median follow-up from treatment initiation was 9.9 months. The estimated one-year event-free survival (EFS) was 77.9% (95% CI 73.8-81.4), and the one-year overall survival (OS) was 90.0% (95% CI 86.5-92.5).
Regarding transportability, 320 patients were extracted from REALYSA who fulfilled the main inclusion criteria of the POLARIX trial and were treated with R-CHOP. The POLARIX-like (PL) population seemed comparable to the R-CHOP arm population of the POLARIX trial, with median ages of 67 years versus 66 years and International Prognostic Index (IPI) scores of 3-5 in 65.7% versus 62%, respectively. The overall response rates were 89% in the PL population and 84% in the POLARIX R-CHOP arm. The one-year progression-free survival rates were 79.8% (95% CI 75.9-83.6) in the PL population and 79.8% (95% CI 73.9-84.4) in the R-CHOP control arm of POLARIX. The characteristics of the 59 patients selected from REALYSA to represent the SENIOR-like (SL) cohort were similar to those in the control arm of the SENIOR trial. The median ages were 83.4 years versus 83.0 years, the rates of performance status scores of 2-4 were 28.8% versus 28.0%, and an IPI score of 3-5 was seen in 79.0% versus 75.0%, respectively. The one-year EFS was 64.5% (95% CI 47.8-77.0) in the patients of the SL population and 60.0% (95% CI 50.8-68.1) in the reduced-dose R-CHOP arm of the SENIOR trial. The one-year OS was 78.3% (95% CI 61.4-88.5) and 78.5% (95% CI 70.2-84.7), respectively.
REALYSA shows promise “for a multitude of different applications, including a better characterization of the lymphoma population in France, as well as innovative study designs, including — but not restricted to — new outcome endpoints or the creation of synthetic control arms,” the authors concluded.
However, the authors noted that ensuring the data quality in a large prospective observational cohort “is extremely challenging.” They suggested that tailored processes are needed to guarantee “effective data management and validation. Furthermore, data collection needs to be regularly updated to keep up with changes in clinical practice.”
Limitations to the study included the short follow-up, the descriptive analysis, and the different imaging techniques used to assess treatment response (i.e., positron emission tomography scans in the SL population versus computerized tomography scans in the SENIOR control arm). The researchers suggested further work, including adjusting variables that affect outcomes and using data with longer follow-up, to confirm these preliminary results.
Any conflicts of interest declared by the authors can be found in the original article.
References
- Ghesquierès H, Cherblanc F, Belot A, et al. Challenges for quality and utilization of real-world data for diffuse large B-cell lymphoma in REALYSA, a LYSA cohort [published online ahead of print, 2023 Oct 24]. Blood Adv. doi: 1182/bloodadvances.2023010798.
- Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351-363.
- Oberic L, Peyrade F, Puyade M, et al. Subcutaneous rituximab-miniCHOP compared with subcutaneous rituximab-miniCHOP plus lenalidomide in diffuse large B-cell lymphoma for patients age 80 years or older. J Clin Oncol. 2021;39(11):1203-1213.
