Early PET response for relapse prediction in 2nd or higher line lisocabtagen maraleucel in large B-cell lymphoma

Abstract Introduction: Anti-CD19 CAR-T-cell therapy (CART) is highly effective in relapsed/refractory (r/r) large B-cell lymphoma (LBCL) and has a curative potential in otherwise dire cases. A plethora of pretreatment factors are associated with the outcome after CART (e.g. lactate dehydrogenase (LDH) and Eastern Cooperative Oncology Group (ECOG) performance status (PS)). Recently, early fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging after CART as assessed by 5-point Deauville score (DS) has been shown to provide predictive information and might help to guide treatment decisions in LBCL pts. However, thus far, most analyses on the prognostic performance of an early FDG-PET after CART derive from patients treated with axicabtagen ciloleucel (Kuhnl et al., ICML 2025), while data on lisocabtagen maraleucel (liso-cel) remain sparse. This study aimed at the analysis of the prognostic potential of early FDG-PET and DS assessment in 2L and ≥3rd line (3L+) liso-cel CART treatment. Methods: We included r/r LBCL pts treated with liso-cel between October 2022 and June 2025 with 1 month (M1) PET DS response data available in a single institution. Response assessment was done locally following the Lugano criteria. The institution's FDG-PET scan scheduling recommendation after CART was at 1 month and 3 months (mos). Patients achieving a metabolic complete response (DS1-3) had additional cross-sectional imaging in case of suspected relapse only. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan Meier estimates. PFS and OS probabilities were compared by log-rank test. Multivariate analysis for PFS and OS including the factors age, CRP, LDH normal versus >upper level normal (ULN), IPI score at liso-cel infusion, DS1-3, DS4-5 partial response (PR)/stable disease (SD) was done by Cox regression. Results: We identified 57 pts (median age (mAge) 63 years (y) [26-84], 43.8 % female (f), 56.2 % male (m), IPI score at liso-cel infusion >2 in 26 pts 45.6 %, LDH at liso-cel >ULN in 10 pts 17.5 %, 50.9% liso-cel as 2L treatment, median follow-up was 4.1 and 9.5 mos for PFS and OS, respectively. Median PFS (mPFS) and OS (mOS) were not reached. 1-year (1y) PFS and OS were 57.3% and 77.9%, respectively. Out of all 57 pts, 29 pts [50.8 %] had DS1-3, 14 pts [24.6 %] had DS4-5 PR/SD and 14 pts [24.6 %] had DS4-5 progressive disease (PD) in M1. The DS1-3 and DS4-5 PR/SD pts had 1y PFS of 83.1% and 57.8% and 1y OS of 90.5 % and 92.8%, respectively. In pts with DS4-5 PD 1y OS was 35.4%. To assess the predictive performance of early PET (M1) restaging after CAR, we focused on patients without PD at PET M1 (43 pts, 75.4%). PFS post liso-cel was significantly associated with DS response categories, with significantly inferior survival in DS4-5 with PR or SD versus DS1-3 [PFS: HR 0.2882 (0.06557-1.267) (p=0.0472)], whereas OS was not associated with DS categories [OS: HR 0.9666 (0.08643-10.81) (p=0.9778)]. In multivariable analysis, DS4-5 vs. DS1-3 was significantly associated with inferior PFS post-CART (HR 4.307 (1.042-20.60) (p=0.0470), whereas there was no significant impact of other factors on PFS (age, CRP, LDH normal versus >upper level normal (ULN), IPI at liso-cel infusion). In addition, we descriptively analysed the response conversion rates from M1 to M3 PET in pts with DS4-5 PR/SD. Of 14 pts with DS4-5 PR/SD M1, only 2 pts [14.3 %] had conversion to DS1-3 CR at M3 without further therapy, 4 pts [28.6 %] remained in PR in M3, as well as 1 pt [7.1] remained in SD in M3, whereas 4 pts [28.6 %] progressed to DS4-5 PD at M3. 3 pts [21.4 %] had their M3 PET response pending. Conclusion: Early PET assessment in patients treated with liso-cel may have the potential to predict long-term remission and could influence early post-CART therapy decision with respect to response-adaption.