December 9, 2023
By Dibash Kumar Das, PhD
In an innovative endeavor aimed at surmounting the hurdles of conducting clinical trials for untreated diffuse large B-cell lymphoma (DLBCL) among the elderly, a team of French researchers led by Benoît Tessoulin, MD/PhD, has unveiled a promising strategy involving synthetic control arms (SCA) generated from a blend of historical clinical trial data and real-world evidence. This approach aims to create more innovative and efficient randomized trials while including the often-excluded population of patients aged over 80 years.
DLBCL, the most common lymphoid malignancy in older individuals, often affects patients aged over 80 years, yet a significant portion of clinical trials tend to exclude this age group, limiting advancements in treatment for this demographic. The gold-standard treatment for untreated DLBCL in patients over 80, rituximab (R) + miniCHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), yields an overall survival (OS) rate of approximately 60 percent at 2 years. Improving outcomes for this frail population remains a considerable challenge.
The study, presented at the 65th ASH Annual Meeting and Exposition leveraged three clinical trials involving patients over 80 years treated with anti-CD20 + miniCHOP regimens (Abstract 72). Two Phase II trials, LNH03-7B and LNH09-7B, provided data for SCA patients, assessing the efficacy of six anti-CD20 + miniCHOP treatments. The SENIOR trial, a Phase III randomized trial comparing R-miniCHOP to R-miniCHOP + lenalidomide, demonstrated no significant differences in OS between the two arms.
The researchers amalgamated this clinical trial data with real-world evidence from the prospective REALYSA (REal world dAta in LYmphoma and Survival in Adults) cohort comprising patients with at least 18 months of follow-up treated with R-miniCHOP. Exclusion criteria were applied to ensure the integrity of the dataset.
Propensity scores were utilized for matching patients between groups based on relevant baseline covariates, using sophisticated statistical methodologies to ensure accurate comparisons. The study demonstrated that well-matched SCAs from historical CTs data replicated SENIOR trial results in DLBCL patients >80 years old, showing similar OS comparisons (HR= 0.996 for SENIOR, HR= 0.98 for SCA-CT), noted Benoit Tessoulin, MD, PHD, of the Hematology Department at the Centre Hospitalier Universitaire de Nantes (CHU Nantes) in France.
Furthermore, matching procedures utilizing real-world data patients were equally effective, showcasing comparable OS trends to the SCA constructed from clinical trial data and the internal control arm of the SENIOR trial, according to Tessoulin. The study highlighted potential limitations due to the loss of power during the matching process, which could be mitigated by adjusting the patient pool balance.
“These compelling findings pave the way for a more robust and inclusive approach to clinical trials in DLBCL among elderly patients, showcasing the potential of synthetic control arms in facilitating more innovative and efficient randomized trials. Further insights and complementary data are anticipated to be presented during upcoming meetings, promising additional depth and perspective to this pioneering research endeavor,” Tessoulin concluded during the presentation.
Dibash Kumar Das is a contributing writer.