Background The use of CD3-CD20-directed bispecific antibodies (BsAb) has significantly improved the outcomes of patients (pts) with relapsed/refractory (r/r) large B-cell lymphoma (r/r LBCL). However, as some patients do not respond to a BsAb treatment or relapse after an initial response, the evaluation of factors determining response to BsAb therapy is of particular importance. The objective of this study was to investigate the prognostic role of FDG-PET- parameters at baseline and at first follow-up in r/r LBCL pts who underwent BsAb treatment.

Methods This is an FDG-PET-based analysis of pts with LBCL undergoing treatment with BsAB from three university centers in Germany (Münster, Essen) and Switzerland (Bern). 54 pts with available baseline FDG-PET scans, and 45 pts with at least one follow-up FDG-PET after initiation of BsAB therapy with a median time of 3.2 months (mo) were included.

FDG-PET standardized uptake values (SUV- peak, max, mean, min), 40% SUVmax based metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were investigated in both FDG-PET scans. Delta FDG-PET parameters were analyzed as a quotient of follow-up FDG-PET and baseline FDG-PET in percentage. Baseline and Delta parameters were analyzed using the Max.stat statistical test in R studio for the optimal cut-off for defining a low-risk and high-risk group for predicting PFS and OS in Kaplan-Meier analysis and Cox regression.

Results Out of 54 enrolled pts, 39 (72%) had diffuse large B-cell lymphoma (DLBCL), and 15 (28%) were diagnosed with high-grade B-cell lymphoma (HGBL). The median number of therapy lines prior BsAb was 3. ORR to BsAb was 46% (CR 24%/PR 22%). After a median follow-up of 13 mo, the median progression-free survival (mPFS) was 3 mo and the median overall survival (mOS) was 7 mo respectively.

Considering obtained SUVpeak values in baseline FDG-PET scans, the cut-off value < 7.9 stratified pts into low-risk (n = 11) and high-risk groups (n = 43) for PFS analysis. The low-risk group had a significant reduced probability for progression (Hazard Ratio (HR): 0.26, P = 0.008). The median PFS of the high risk-group was 2 mo, while not reached in the low-risk group at the end of follow-up (P = 0.017).

Noteworthy, the baseline SUVmin cut-off below 4.04 was highly significant in the low-risk group (n = 19) vs. high-risk group (n = 35) for the decrease in mortality risk (HR: 0,24, P = 0.003). While the MTV was not significant in distinguishing mortality risk, the TLG cut-off below 1508.5 revealed a reduced mortality risk for the low-risk group (HR: 0.43, P = 0.04, n = 35).

In the first follow-up FDG-PET a total of 20 (44%) pts demonstrated PD and were excluded for the PFS-analysis. In analogue to the baseline PET, a SUVpeak reduction with a cut-off of 49.5% assigned pts in the low-risk (n = 17) and high-risk (n = 8) group. Low-risk pts demonstrate a significant lower probability of relapse (HR: 0.06, P = 0.002, n = 25). The median PFS for high- vs low-risk group was 3 vs 33 mo (P = 0.001). Pts with complete metabolic response (DS1-3, n = 9) had a significant improved PFS with no further event at the end of follow-up in comparison to pts with incomplete metabolic response (PR/SD) DS4 (n = 10; mPFS 5 months) and DS5 (n = 11; mPFS 2 months; P < 0.001).

All investigated Delta parameters show a significant risk prognostication for OS (all log rank P < 0.0001, n=45). In terms of SUVmax, pts in the low-risk group (n = 19) presenting with at least 29,6% SUVmax reduction revealed a significant lower mortality risk (HR: 0.11, P < 0.0001): mOS not reached vs. 6 mo in the high-risk group. Risk-stratification based on DS was not superior in predicting OS compared to Delta parameters, e.g. DS1-3 vs DS4-5 (P = 0.02).

Conclusion MTV at BsAb initiation was not predictive for the outcomes while higher metabolic activity (SUVpeak and SUVmin) is associated with a higher risk for progression and worse survival.

In first follow-up FDG-PET, a significant decrease in metabolic activity (SUVpeak) is associated with a lower risk of progression.

Finally, BsAb should not be withheld for patients with high MTV. First FDG-PET response assessment is crucial for the subsequent prognosis of patients undergoing BsAb treatment.

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2025
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