Page 168 - Haematologica Vol. 109 - July 2024

ARTICLE - MAIC in 3L+ FL M.J. Maurer et al.
Figure 2. Kaplan-Meier curve of progression-free survival for LEO CReWE versus GO29781 trial. CI: Confidence Interval; N: num- ber; PFS: progression-free survival.
within LEO CReWE identified that 54-64% of relapses to front-line therapy for FL were detected clinically.17 A distinct advantage of the LEO consortium is the involvement of ex- perts in lymphoma clinical trials and patient management, including leaders in the NCTN and several members of the NCI Lymphoma Steering Committee, who have expertise in lymphoma response assessment.
Despite these commonly cited limitations for synthetic co- horts, several recent studies18-20 have used this strategy to support the impact of phase II trials in lymphoma. Our study differs notably from the others by demonstrating modest differences between the measured outcomes of the phase II trial results and the synthetic cohort. There are several possible explanations for this difference, including the unique choice of MAIC methodology to accommodate lack of IPD from GO29781, the line of index therapy or variables chosen for matching, improved assessment of outcomes and/or improved outcomes in an observational cohort managed by lymphoma experts, or the true relative activity of mosunetu- zumab compared to other options in this patient setting. The generation of a synthetic cohort and/or implementation of a matching-based analysis requires a series of decisions that may influence the results. Analytical decisions such as eligibility criteria, selection of index therapy, and matching variables are then applied to the cohort selected for the analysis. We performed a series of sensitivity analyses to
address the uncertainty in estimation of outcomes intro- duced by such decisions. Selecting the cohort and index line is especially critical given the heterogeneity in treatment selection and expected outcomes for patients with R/R FL. The index line of therapy for LEO CReWE was chosen based on the line of therapy most like the clinical charac- teristics of the GO29781 trial based on MAIC weights. Our initial publication of the LEO CReWE FL cohort primarily focused on outcomes in patients at initial time of eligibility for the GO29781 trial (i.e., third line or beyond with prior anti-CD20 and alkylator therapy), with 94% of patients achieving this in the third line setting.9 However, utilizing the first eligible line in our sensitivity analysis resulted in essentially unusable results due largely to imbalances in the number of prior lines of therapy. This highlights the importance of careful examination of clinical characteristics and thoughtful alignment of a synthetic cohort with clinical trial criteria. In contrast, alternative collections of matching variables and trial inclusion / exclusion criteria had little impact on effective sample size or weighted outcomes.
Conclusions
These results support our previously published data showing that, despite multiple recurrences, patients
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