ABCL-334 Long-term survival projections of loncastuximab tesirine-treated patients in relapsed or refractory diffuse large b-cell lymphoma

Abstract

CONTEXT: Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca) is an FDA-approved CD19-directed antibody-drug conjugate for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). From the LOTIS-2 trial primary data cut (April 6, 2020), overall response rate was 48.3% and median overall survival (OS) was 9.9 months. The OS Kaplan-Meier (KM) plot displayed a survival plateau suggesting presence of long-term survivors (LTS).

OBJECTIVE: Estimate percentage of LTS and expected lifetime survival (mean OS) for Lonca-treated patients.

DESIGN: Survival analysis included parametric, flexible cubic spline, mixture cure, and non-mixture cure models, which were fit utilizing multiple distributions. Age- and gender-matched United States life table hazards were used in generating LTS projections to ensure the modeled hazards were not less than in the general population. Best-fit models were determined through fit statistics, KM and fitted curve overlays, and clinical plausibility. The best-fit model from each method was selected for overall best fit. A hybrid model, following the best-fit parametric/spline model to a defined time point and switching to general population mortality, was also constructed.

SETTING: The LOTIS-2 study (NCT03589469) is a single-arm, open-label, phase 2 study of 145 adults with R/R DLBCL after ≥2 prior treatments.

INTERVENTIONS: Intravenous Lonca (150 µg/kg for two cycles, 75 µg/kg thereafter) for up to 1 year or until disease relapse/progression.

MAIN OUTCOME MEASURES: Percentage of LTS estimated via statistical models and estimated lifetime survival (mean OS).

RESULTS: Mixture and non-mixture cure models fit observed data well. Due to better fit than parametric models, spline models were used in the hybrid model. Mixture and non-mixture cure estimated LTS as 24%-26%. Mixture cure, non-mixture cure, and hybrid model with 2-year switch point provided consistent OS predictions (6.11-6.23 years). Sensitivity analysis of the hybrid model with a 3-year switch point estimated shorter survival (4.96 years) with a switch point below the observed survival plateau.

CONCLUSIONS: The observed survival plateau suggests Lonca-treated patients may include LTS. Multiple models fit the trial data well and align on survival projections. Additional follow-up may help refine the switch point of the hybrid model and confirm presence of LTS. ©2022 American Society of Clinical Oncology, Inc. Reused with permission. All rights reserved.