Page 167 - Haematologica Vol. 109 - July 2024

ARTICLE - MAIC in 3L+ FL
M.J. Maurer et al.
ters and clinical contexts similar to those for the GO29781 trial, with 40% of patients receiving index therapy on a clinical trial, which is distinct from observational studies involving cohorts of patients with R/R FL from general practices.12-14 MAIC rebalanced the LEO CReWE cohort to align with the clinical characteristics of patients enrolled on the GO29781 trial. Standard limitations of these types of comparative effectiveness studies apply, including po- tential bias by both observed and unobserved differences in the patients between the two cohorts. Adverse event data were not available in the LEO CReWE cohort, and thus this study does not provide clinical comparisons of toxic- ity or tolerability. Safety profiles and quality of life should be considered when making clinical decisions regarding therapy in this clinical space.
Individual patient-level data (IPD) from GO29781 were not available for this analysis, and thus the weighting of the LEO CReWE data was based on the summary statistics for the GO29781 trial data as opposed to matching or propensity weighting approaches utilizing IPD. The MAIC approach utilized in this study weighted the individuals in the LEO CReWE cohort such that the key clinical charac- teristics used for matching were balanced between the LEO CReWE and GO29781. Using this approach, all eligible patients from the LEO CReWE cohort were utilized in the analysis, but LEO CReWE patients with disparate clinical characteristics compared to the GO29781 trial participants contributed less information to the analysis compared to LEO CReWE patients with similar clinical characteristics as the GO29781 trial. Methods for checking fit and calibra- tion in a MAIC weighting approach are limited compared to traditional propensity score weighting, in which IPD is available. Additionally, residual confounding may remain after MAIC weighting.
Response rates observed in the LEO CReWE cohort (weight- ed ORR=73%, CR=53%) were encouraging for R/R FL, yet remained lower than those observed in the GO29781 study (ORR=80%, CR=60%). PFS at 12 months was similar be- tween the LEO CReWE cohort and GO29781 trial based on the reported duration of follow-up used in this analysis. Notably, response rates (ORR=76%, CR=56%) were higher and PFS12 (57%) was lower for LEO CReWE index therapies received on clinical trial, though this may be confounded by patient selection and varying response rates of different treatment classes. Response and progression are assessed differently between clinical trials and routine clinical prac- tice, which needs to be considered in the interpretation of these results. Clinical trials feature frequent and standard- ized disease assessment that includes imaging at regular intervals. In routine clinical care, intervals for response assessment are not stringently dictated, and imaging may not necessarily be performed on a regular schedule. Fur- ther, clinicians may not universally confirm response with repeat bone marrow biopsy (BMB) in patients who had prior bone marrow involvement, and clinical plans to proceed to
Figure 1. Analysis flow chart. I / E: inclusion / exclusion; MAIC: matching-adjusted indirect comparison; N: number; PFS: progres- sion-free survival.
transplantation based on response may influence decision making. In the GO29781 trial, a BMB was required at study entry with repeat BMB to confirm complete response if bone marrow involvement was present at baseline. This was not required in the LEO CReWE cohort and only 41% of patients had bone marrow biopsied at the start of index therapy (data not shown). However, in an analysis of 580 patients pooled from 7 National Clinical Trials Network (NCTN) clinical trials of FL, Rutherford and colleagues identified that BMB were irrelevant to assessing complete response in 99% of patients.15 Thus it is unlikely that dif- ferences in routine BMB between trial and observational cohorts has a significant impact on the interpretation of results. Unlike aggressive lymphoma, where progression often manifests clinically prior to planned imaging,16 routine imaging on clinical trials may contribute to shorter PFS in the setting of FL (as compared to observational studies without routine imaging) when an increase in tumor size may not correspond to a clinical indication for evaluation or subsequent therapy. A prior study from three centers
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