Potential surrogate endpoint for B-cell hematologic malignancy: A systematic review and meta-analysis.

Confirming the patient benefit of progression-free survival (PFS) in B-cell non-Hodgkin lymphoma (B-NHL) and multiple myeloma (MM) has become increasingly challenging due to the improved outcomes brought by novel therapies. In parallel, the U.S. Food and Drug Administration recommends conducting randomized trials, focusing on evaluating early endpoints to compare study and control arms for accelerated approval (AA). From both the clinical and regulatory perspectives, identifying early surrogate endpoints for PFS is imperative. In principle, the complete response rate (CRR) is a potential early endpoint for granting AA. This study aimed to evaluate whether the CRR is a surrogate early endpoint for PFS in patients with B-cell malignancies. We investigated the results of randomized trials with data on CRR and PFS using a combined approach of PubMed and Clinical Trial.gov (CTG), identifying 52 trials after applying exclusion criteria. A meta-regression plot showed a significant correlation between the CRR and PFS with an R-squared of 0.822 in 13 trials of aggressive B-NHL, 0.941 in the 8 trials of indolent N-NHL and 0.492 in the 31 trials of MM. This meta-analysis suggests that the CRR can be considered an early surrogate endpoint for PFS in B-NHL and MM.