Massachusetts General Hospital Bellingham, MA, United States
H. Ababneh1, M. J. Frigault2, A. K. Ng3, and C. G. Patel1; 1Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2Massachusetts General Hospital/ Harvard Medical School, Boston, MA, 3Dana Farber Cancer Institute, Boston, MA
Purpose/Objective(s): To evaluate the prognostic value of quantitative positron emission tomography/computed tomography (PET/CT) parameters on the outcomes in large B-cell lymphoma (LBCL) patients following CAR T-cell therapy failure. Materials/
Methods: Thirty-three patients who had PET-CT scans done post-CAR T failure and received salvage therapies were retrospectively identified and analyzed in a single institution database of LBCL patients treated with CD19-targeted CAR T-cell therapy. All salvage therapies were defined at the time of the first salvage therapy following CAR T-cell therapy failure. The predictive and prognostic values of low vs. high metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) for categorical study endpoints were analyzed with cutoff values determined using receiver operating characteristic curves according to the Youden index, whereas the optimal cutpoints for survival endpoints were estimated by using maximally-selected rank statistics. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method. Results: A total of 33 LBCL patients who had PET-CT scans done post-CAR T failure and then received salvage therapies as a first salvage modality [radiation therapy (RT), 9 patients; combined modality therapy, 7 patients; systemic therapy, 17 patients] were analyzed. The median follow-up after CAR T-cell infusion was 11.7 months [interquartile range (IQR): 5.1-24.4 months], ], and the median follow-up after post-CAR T salvage therapy was 7.3 months (IQR: 2.7-19.1 months). The median timeframe for the PET scan done post-CAR T failure was 2.4 months (IQR: 0.96 -5.0 months). On univariate analysis, high MTV and TLG were associated with inferior OS (HR=8.4, p < 0.0001; HR=3.2, p= 0.01, respectively). High MTV was associated with a non-significant trend of inferior PFS (HR=3.5, p= 0.09). High SUVmax did not predict for inferior OS or inferior PFS. Low post-CAR T MTV was also associated with a non-significant trend of improved overall response (complete response-CR and partial response) following the first salvage therapy (OR=8.6, p=0.06). On multivariate analysis, high MTV (HR=4.5, 95% CI: 1.5-13.8, p=0.007) and high IPI at the time of salvage therapy (HR=2.9, 95% CI: 1.0-8.5, p=0.04) were identified to be independent prognostic factors for inferior OS. In a subgroup analysis of patients who received salvage RT (n=13), low MTV was associated with a non-significant trend towards improved in-field response (p=0.06). Conclusion: Our study demonstrates that quantitative measurements of post-CAR T tumor metabolic burden, particularly MTV, significantly predict worse OS in relapsed/refractory LBCL patients. These findings underscore the potential of quantitative PET-CT parameters in guiding therapy following CAR T-cell therapy failure.
