Loncastuximab Tesirine Versus Glofitamab for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy: A Matching-Adjusted Indirect Comparison

OBJECTIVES: Relapsed and refractory (R/R) diffuse large B-cell lymphoma (DLBCL) prognosis is particularly poor for patients after ≥2 systemic therapies. Loncastuximab tesirine (loncastuximab) and glofitamab have been recently approved in this setting and the lack of head-to-head trials requires an indirect comparison to evaluate their relative efficacy and safety.

METHODS: A systematic literature review identified single-arm trials LOTIS-2 and NP30179 as providing relevant trial data for comparison and unanchored matching-adjusted indirect comparisons (MAICs) were conducted. To reduce potential bias associated with the cross-study comparisons, baseline variables with potential prognostic impact were adjusted to generate matched patient characteristics. Endpoints of interest were response rates (overall [ORR], complete [CR] and partial [PR]), duration of response (DOR), duration of CR (DOCR), progression-free survival (PFS), overall survival (OS), and key safety outcomes.

RESULTS: No evidence of treatment differences was observed between loncastuximab and glofitamab for ORR, DOR, DOCR, PFS, and OS. Patients treated with glofitamab had greater odds of achieving a CR, but this did not lead to differences in long term endpoints such as PFS and OS. Safety results significantly favored loncastuximab for serious adverse event (SAE) cytokine release syndrome (CRS), and significantly favored glofitamab for grade 3-4 gamma-glutamyl transferase elevation and thrombocytopenia. Loncastuximab was associated with numerically higher odds of grade 3-4 anemia, and glofitamab with numerically higher odds of infections, although neither were significant. There were no notable differences between treatments for fatal AEs and SAEs.

CONCLUSIONS: While accounting for the known MAIC limitations, in R/R DLBCL patients after ≥2 systemic therapies, these analyses show no evidence of a difference between the treatments for all assessed efficacy endpoints (ORR, PR, DOR, DOCR, PFS, OS), except CR which was higher with glofitamab. Safety comparisons show few differences between the treatments, in line with their known safety profiles.