OBJECTIVES : In the single-arm phase 2 L-MIND trial (NCT02399085), NTE R/R DLBCL patients receiving T-L demonstrated sustained response. Without a comparator arm, unanchored MAICs can be used to compare the overall survival (OS) and the progression free survival (PFS) of patients receiving T-L and SoC options. The objective of this analysis was to evaluate the comparative efficacy of T-L versus the combination of: bendamustine with rituximab (B-R); polatuzumab vedotin with B-R (P-B-R); rituximab with prednisolone, etoposide, chlorambucil, lomustine (R-PECC); or versus lenalidomide monotherapy (L-mono).

METHODS : A systematic literature review was conducted. Six treatment arms from 5 studies with similar inclusion and exclusion criteria, designs and outcomes definitions compared to L-MIND were included in the comparisons. Populations were matched for all clinically validated effect modifiers and prognostic factors with available data in published studies, as per NICE guidelines. Treatment effects were quantified by constant or time-dependent hazard ratios (HR) estimated from Cox models, depending on whether the assumption of proportionality of hazards was met. HRs were pooled when several sources were available for a comparator.

RESULTS : HRs, 95% confidence intervals, and p-values, for OS and PFS, were respectively: 0.39 (0.18, 0.82) [0.014] and 0.39 (0.29, 0.53) [<0.001] versus B-R; 1.82 (0.58, 5.65) [0.302] and 1.42 (0.65, 3.09) [0.376] in the first 4 months of follow-up versus P-B-R, and 0.41 (0.19, 0.90) [0.026] and 0.39 (0.14, 1.06) [0.065] after 4 months of follow-up versus P-B-R; 0.51 (0.29, 0.90) [0.02] versus R-PECC (no PFS available for R-PECC); and 0.41 (0.22, 0.76) [0.005] and 0.55 (0.31, 0.97) [0.04] versus L-mono.

CONCLUSIONS : The available data and the MAICs suggest that NTE R/R DLBCL patients receiving T-L can experience significantly better health outcomes than patients receiving the identified SoC comparators. The MAIC results should be interpreted with caution owing to known methodological limitations of unanchored comparisons.