Semiquantitative PET Parameters Refine Prognosis in CAR T-Treated Lymphoma After 1 and 3 Months: A Prospective...

Chimeric antigen receptor T-cell (CAR T) therapy has shown remarkable efficacy in treating relapsed or refractory large B-cell lymphoma. However, for nearly half of these patients, the therapy eventually does not achieve durable remission. We investigated whether semiquantitative PET parameters (namely, SUV_max, metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) could improve risk stratification 1 mo (PET1m) and 3 mo (PET3m) after CAR T infusion. Methods: In this prospective, single-center cohort study, patients with large B-cell lymphoma received axicabtagene ciloleucel or tisagenlecleucel. [¹⁸F]FDG PET/CT scans were acquired at baseline, 1 mo, and 3 mo after infusion. MTV and TLG were calculated using a threshold SUV_max of 4 or greater. Patients were followed for overall survival (OS), progression-free survival (PFS), and duration of response (DoR). The imaging assessment was based on the Lugano recommendation for response assessment. Prognostic factors were identified using univariate and multivariate Cox regression. Results: Sixty-one patients were enrolled, with a median follow-up of 18 mo. Twenty-eight (46%) patients died. Kaplan-Meier analysis with log-rank tests indicated a significant association of elevated Deauville score (DS), SUV_max, MTV, and TLG with OS (all P < 0.05). DS cutoff was arbitrarily fixed at 4. The optimal SUV_max, MTV, and TLG cutoffs at PET1m were 9.1, 60.8, and 97.0, respectively; whereas at PET3m, they were 6.3, 120.1, and 436.9, respectively. Patients with an SUV_max of 6.3 or greater at PET3m had an 8-fold increase in risk of death (hazard ratio [HR], 8.15; 95% CI, 2.81-23.6; P < 0.01) compared with those below this cutoff. Similarly, higher MTV (≥120.1) at PET3m yielded a nearly 10-fold risk (HR, 9.87; 95% CI, 3.65-26.7; P < 0.01). DS, SUV_max, MTV, and TLG at both PET1m and PET3m were associated with OS and PFS (all P < 0.05), whereas PET3m parameters also correlated with DoR (P < 0.05). Harrell C-index values were higher for PET3m measures than for PET1m, though differences were not statistically significant (P > 0.05). On multivariable analysis, older age (HR, 1.10), bridging therapy (HR, 10.91), elevated lactate dehydrogenase (HR, 6.43), increased fibrinogen (HR, 5.27), and higher SUV_max at PET3m (HR, 11.03) independently predicted poorer OS. There were no significant associations between SUV_max, MTV, and TLG with CAR T-related toxicities. Conclusion: Semiquantitative PET parameters, such as SUV_max, MTV, and TLG, at 1 mo and 3 mo after CAR T-cell therapy correlate significantly with OS, PFS, and DoR. [¹⁸F]FDG PET/CT at 3 mo may offer slightly stronger prognostic discrimination, but both time points can be used for early risk stratification.