1088 - Prognostic Significance of Baseline Metabolic Tumor Volume in Relapsed/Refractory Aggressive B-cell Lymphoma Patients Treated with Bispecific Antibodies: A Multi-Institution Discovery-Validation Study
Presenter(s)
B. A. Johnson1, P. E. Perez2, J. Y. Nakashima3, D. De Avila4, S. Gaballa4, J. Pinilla4, O. C. Puglianini5, J. C. Chavez6, H. Mahadevia6, J. Munoz7, M. Tsang7, Y. Wang8, C. Tiger8, D. Li9, F. L. Locke5, M. D. Jain5, B. S. Hoppe1, Y. Zhang4, M. Iqbal6, and N. B. Figura3; 1Mayo Clinic, Department of Radiation Oncology, Jacksonville, FL, 2Morsani College of Medicine at the University of South Florida, Tampa, FL, 3H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 4H. Lee Moffitt Cancer Center and Research Institute, Department of Malignant Hematology, Tampa, FL, 5H. Lee Moffitt Cancer Center and Research Institute, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Tampa, FL, 6Mayo Clinic, Division of Hematology, Jacksonville, FL, 7Mayo Clinic, Division of Hematology, Phoenix, AZ, 8Mayo Clinic, Division of Hematology, Rochester, MN, 9Mayo Clinic, Department of Laboratory Medicine and Pathology, Jacksonville, FL
Purpose/Objective(s): Bispecific antibodies (BsAbs) targeting CD20 have transformed the treatment of relapsed/refractory (R/R) aggressive B-cell lymphomas, yet biomarkers predicting efficacy remain poorly defined. We investigated whether baseline metabolic tumor volume (MTV) predicts progression-free survival (PFS) and overall survival (OS) in R/R aggressive B-cell lymphoma patients who received treatment with BsAbs.
Materials/Methods: We retrospectively analyzed 169 R/R aggressive B-cell lymphoma patients treated with BsAbs (epcoritamab n = 86, glofitamab n = 43, mosunetuzumab+polatuzumab n = 40) across two academic institutions. Baseline PET/CT was performed within 90 days of first BsAb infusion. MTV was calculated using a liver SUVmean plus two standard deviations threshold. The optimal MTV cutoff was derived from Institution 1 (n = 102) using ROC analysis with the Youden index (12-month PFS) and independently validated in Institution 2 (n = 67). Kaplan-Meier estimates were performed with log-rank testing and multivariable Cox regression adjusting for age, sex, LDH, prior therapy lines, and prior CAR-T exposure. Formal interaction testing was also conducted.
Results: Median age was 68 years (range 22–89); 69% were male; median number of prior lines of therapy was 3 (range 1–11); 57% had prior CAR-T exposure. Median follow-up was 22.6 months (reverse Kaplan-Meier), and the median pretreatment MTV was 228 cc (IQR 68–660). ROC analysis identified an optimal MTV cutoff of 111 cc (AUC 0.698), validated in the independent cohort with a higher AUC (0.761). High MTV (=111 cc, n = 108) was associated with markedly inferior PFS (median 3.0 vs 23.3 months, P < .0001) and OS (median 6.5 vs 51.8 months, P < .0001) when compared to low MTV (<111 cc, n = 61). On multivariable analysis, log-transformed MTV independently predicted both PFS (HR 1.26, 95% CI 1.12–1.42, P = .0002) and OS (HR 1.38, 95% CI 1.20–1.59, P < .0001). MTV significantly stratified outcomes for epcoritamab and mosunetuzumab+polatuzumab (both P < .003), with a consistent trend for glofitamab (PFS P = .054). High MTV combined with elevated LDH identified an ultra-high-risk subgroup (median PFS 2.3 vs 27.5 months for low MTV/normal LDH). Interaction testing confirmed additive rather than synergistic effects (P > .05).
Conclusion: Baseline MTV is an independently validated predictor of PFS and OS in R/R aggressive B-cell lymphoma patients treated with BsAbs. An MTV threshold of 111 cc robustly stratifies outcomes across institutions and agents. Tumor burden may inform pre-treatment risk assessment to guide patient selection for BsAb therapy.