Prognostic value of baseline and early response FDG-PET/CT in patients with refractory and relapsed aggressive B-cell lymphoma undergoing CAR-T cell therapy

Abstract

Purpose Chimeric antigen receptor (CAR)-T cells are a viable treatment option for patients with relapsed or refractory (r/r) aggressive B-cell lymphomas. The prognosis of patients who relapse after CAR-T cell treatment is dismal and factors predicting outcomes need to be identified. Our aim was to assess the value of FDG-PET/CT in terms of predicting patient outcomes. Methods Twenty-two patients with r/r B-cell lymphoma who received CAR-T cell treatment with tisagenlecleucel (n = 17) or axicabtagene ciloleucel (n = 5) underwent quantitative FDG-PET/CT before (PET-0) and 1 month after infusion of CAR-T cells (PET-1). PET-1 was classified as complete metabolic response (CMR, Deauville score 1–3) or non-CMR (Deauville score 4–5). Results At the time of PET-1, 12/22 (55%) patients showed CMR, ten (45%) patients non-CMR. 7/12 (58%) CMR patients relapsed after a median of 223 days, three of them (25%) died. 9/10 (90%) non-CMR patients developed relapse or progressive disease after a median of 91 days, eight of them (80%) died. CMR patients demonstrated a significantly lower median total metabolic tumor volume (TMTV) in PET-0 (1 ml) than non-CMR patients (225 ml). Conclusion Our results confirm the prognostic value of PET-1. 42% of all CMR patients are still in remission 1 year after CAR T-cell treatment. 90% of the non-CMR patients relapsed, indicating the need for early intervention. Higher TMTV before CAR-T cell infusion was associated with lower chances of CMR.

Effective bridging strategies prior to infusion with tisagenlecleucel results in high response rates and long-term remission in relapsed/refractory large B-cell lymphoma: findings from a German monocentric study

“…An early relapse at month 1 following CAR-T infusion detected by PET-CT was associated with a very poor prognosis whereas a complete metabolic remission at month 3 was linked to a favorable survival outcome. These findings, consistent with others, provide a rationale for early PET-CT to predict responses and in the event of progression or relapse, alternative treatments should be applied (Kuhnl et al 2022 ; Georgi et al 2023 ).…”

Effective bridging strategies prior to infusion with tisagenlecleucel results in high response rates and long-term remission in relapsed / refractory large B-cell lymphoma: findings from a German monocentric study.

“…An early relapse at month 1 following CAR-T infusion detected by PET-CT was associated with a very poor prognosis whereas a complete metabolic remission at month 3 was linked to a favorable survival outcome. These ndings, consistent with others, provide a rationale for early PET-CT to predict responses and in the event of progression or relapse, alternative treatments should be applied [34,35].…”

FDG-PET/CT is a powerful tool to predict and evaluate response to chimeric antigen receptor (CAR) T-cell therapy in Non-Hodgkin-Lymphoma (NHL)

“…In addition, we demonstrate that patients with DS ≤ 4 prior CAR T-cell therapy tend towards longer PFS compared to patients with a pretherapeutic DS 5. In line with that, Georgi et al demonstrated, that patients with CMR (DS ≤ 3) on pre-therapeutic FDG-PET/CT had better PFS and tend to had better OS compared to patients with non-CMR (DS > 3) on pre-therapeutic FDG-PET/CT [29]. Further studies are needed to clarify whether a DS ≤ 4 on pre-therapeutic FDG-PET/CT may be used as a valid response predictor prior to therapy.…”