(001) A Novel Methodology for Assessing Response to Lymphoma Treatment using Real World Data – the Real-World Lugano (rwLugano) Study

Background: Real-world evidence to support regulatory review of oncology drugs has included non-interventional studies describing safety and effectiveness in routine care settings and use of historical controls to contextualize safety and efficacy in single-arm trials. In lymphoma clinical trials, blinded independent central review (BICR) per Lugano 2014 criteria is the standard method to assess treatment response. Development and validation of corresponding methods using real-world data (RWD) to accurately classify oncology treatment effectiveness is needed.

Objectives: To develop and assess performance of a novel RWD methodology, real-world Lugano (rwLugano), derived from Lugano 2014 criteria to classify lymphoma treatment response.

Methods: We conducted a retrospective multisite chart review study within Cardinal Health’s Practice Research Network (PRN) to identify adult patients with diffuse large B-cell lymphoma (DLBCL) treated with first line chemoimmunotherapy in US oncology practice (2015-2022). We compared the proportion of patients classified as complete response (CR) using 3 methods: 1) physician-charted response extracted from clinical notes in medical records, 2) rwLugano calculated using data elements, such as Deauville score and standardized uptake value of Lugano 2014 extracted from PET-CT reports, and 3) BICR adjudicated by two lymphoma radiologists using Lugano 2014 criteria facilitated by deidentified digital image transfer. Statistical analyses comprised multivariate generalized linear mixed modeling [Odds Ratio (OR); 95% CI].

Results: The study identified 174 patients with DLBCL (female 41%; White 78%; Hispanic 7%; mean age 66 years) geographically distributed across the US. Assignment of CR at initial response assessment was proportionately lower for physician-charted (64%), compared to rwLugano (83%) and BICR (82%). Compared to CR by BICR, physician-charted (agreement: 76%) resulted in lower estimation of CR (OR=0.22; 95%CI:0.12-0.43), whereas rwLugano (agreement: 86%) was not statistically different (OR=1.2; 95%CI:0.6-2.4).

Conclusions: In this study, physician-charted response, the current standard for lymphoma treatment response assessment using RWD, resulted in proportionally fewer estimates of CR compared to BICR; however, rwLugano classification performed similarly to BICR. The implications of our findings are twofold: First, we demonstrated that BICR is a viable methodology for outcome classification in observational research. Second, rwLugano, a novel measure of lymphoma treatment response, may be a relevant measure of outcome classification studies using RWD; however, further study is needed to validate these findings.