Metabolic characteristics and prognostic differentiation of aggressive lymphoma using one-month post-CAR-T FDG PET/CT.

in Journal of hematology & oncology by William G Breen, Matthew A Hathcock, Jason R Young, Roman O Kowalchuk, Radhika Bansal, Arushi Khurana, N Nora Bennani, Jonas Paludo, Jose C Villasboas Bisneto, Yucai Wang, Stephen M Ansell, Jennifer L Peterson, Patrick B Johnston, Scott C Lester, Yi Lin

TLDR

  • The study found that higher SUVMax levels at one month post-CAR-T therapy are associated with increased risk of cancer progression and death, which may guide treatment decisions.

Abstract

F-18 fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) is used to assess response of non-Hodgkin lymphoma (NHL) to chimeric antigen receptor T cell (CAR-T) therapy. We sought to describe metabolic and volumetric PET prognostic factors at one month post-CAR-T and identify which patients with partial response (PR) or stable disease (SD) are most likely to subsequently achieve complete response (CR), and which will develop progressive disease (PD) and death. Sixty-nine patients with NHL received axicabtagene ciloleucel CAR-T therapy. One-month post-CAR-T infusion and PET/CT scans were segmented with a fixed absolute SUV maximum (SUVMax) threshold of 2.5 using a semiautomated workflow with manual modification to exclude physiologic uptake as needed. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVMax, and other lesion characteristics were calculated and associated with risk of PD and death. Patients with total MTV > 180 cc, presence of bone or parenchymal disease, SUVMax > 10, single lesion TLG > 245 g, or > 2 total lesions had increased risk of death. Patients with total MTV > 55 cc, total TLG > 250 cc, SUV Max > 10, or > 2 total lesions had increased risk of PD. For the subset of 28 patients with PR/SD, higher SUVMax was associated with increased risk of subsequent PD and death. While 86% of patients who had SUVMax ≥ 10 eventually had PD (HR 3.63, 1.13-11.66, p = 0.03), only 36% of those with SUVMax < 10 had PD. Higher SUVMax at one month post-CAR-T is associated with higher risk of PD and death. SUVMax ≥ 10 may be useful in guiding early salvage treatment decisions in patients with SD/PR at one month.

Overview

  • The study aimed to identify metabolic and volumetric PET prognostic factors at one month post-chimeric antigen receptor T cell (CAR-T) therapy for non-Hodgkin lymphoma (NHL) and predict which patients will achieve complete response (CR) or develop progressive disease (PD) and death.
  • The study included 69 patients with NHL who received axicabtagene ciloleucel CAR-T therapy and underwent PET/computed tomography (PET/CT) scans at one month post-infusion.
  • The primary objective was to determine whether SUVMax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other lesion characteristics are associated with risk of PD and death.

Comparative Analysis & Findings

  • Patients with total MTV >180 cc, bone or parenchymal disease, SUVMax >10, single lesion TLG >245 g, or >2 total lesions had increased risk of death.
  • Patients with total MTV >55 cc, total TLG >250 cc, SUVMax >10, or >2 total lesions had increased risk of PD.
  • For patients with partial response (PR) or stable disease (SD), higher SUVMax was associated with increased risk of subsequent PD and death.

Implications and Future Directions

  • Higher SUVMax at one month post-CAR-T is associated with higher risk of PD and death, which may guide early salvage treatment decisions in patients with SD/PR at one month.
  • Future studies could explore the use of SUVMax and other PET parameters in combination with clinical factors to predict treatment responses and outcomes.
  • Additionally, the study's findings could inform the development of novel therapies that target specific patient populations and optimize treatment strategies.
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