Faculty Collaboration Database

PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial. Clin Cancer Res 2024 Jan 05;30(1):139-149

Date

10/19/2023

Pubmed ID

37855688

Pubmed Central ID

PMC10872617

DOI

10.1158/1078-0432.CCR-23-1561

Scopus ID

2-s2.0-85181760711 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

PURPOSE: Significant progress has occurred in developing quantitative PET/CT biomarkers in diffuse large B-cell lymphoma (DLBCL). Total metabolic tumor volume (MTV) is the most extensively studied, enabling assessment of FDG-avid tumor burden associated with outcomes. However, prior studies evaluated the outcome of cytotoxic chemotherapy or chimeric antigen receptor T-cell therapy without data on recently approved FDA agents. Therefore, we aimed to assess the prognosis of PET/CT biomarkers in patients treated with loncastuximab tesirine.

EXPERIMENTAL DESIGN: We centrally reviewed screening PET/CT scans of patients with relapsed/refractory DLBCL enrolled in the LOTIS-2 (NCT03589469) study. MTV was obtained by computing individual volumes using the SUV ≥4.0 threshold. Other PET/CT metrics, clinical factors, and the International Metabolic Prognostic Index (IMPI) were evaluated. Logistic regression was used to assess the association between biomarkers and treatment response. Cox regression was used to determine the effect of biomarkers on time-to-event outcomes. We estimated biomarker prediction as continuous and binary variables defined by cutoff points.

RESULTS: Across 138 patients included in this study, MTV with a cutoff point of 96 mL was the biomarker associated with the highest predictive performance in univariable and multivariable models to predict failure to achieve complete metabolic response (OR, 5.42; P = 0.002), progression-free survival (HR, 2.68; P = 0.002), and overall survival (HR, 3.09; P < 0.0001). IMPI demonstrated an appropriate performance, however, not better than MTV alone.

CONCLUSIONS: Pretreatment MTV demonstrated robust risk stratification, with those patients demonstrating high MTV achieving lower responses and survival to loncastuximab tesirine in relapsed/refractory DLBCL.

Author List

Alderuccio JP, Reis IM, Hamadani M, Nachiappan M, Leslom S, Kahl BS, Ai WZ, Radford J, Solh M, Ardeshna KM, Hess BT, Lunning MA, Zinzani PL, Stathis A, Carlo-Stella C, Lossos IS, Caimi PF, Han S, Yang F, Kuker RA, Moskowitz CH

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biomarkers
Clinical Trials as Topic
Fluorodeoxyglucose F18
Humans
Lymphoma, Large B-Cell, Diffuse
Positron Emission Tomography Computed Tomography
Positron-Emission Tomography
Prognosis
Retrospective Studies
Risk Assessment
Tumor Burden