18F-FDG PET Improves Baseline Clinical Predictors of Response in Diffuse Large B-Cell Lymphoma: The HOVON-84 Study

We aimed to determine the added value of baseline metabolic tumor volume (MTV) and interim positron emission tomography (I-PET) to age-adjusted international prognostic index (aaIPI) to predict 2-year progression-free survival (PFS) in diffuse large B-cell lymphoma (DLBCL). Secondary objectives were to investigate optimal I-PET response criteria (using Deauville score (DS) - or quantitative change in maximum Standardized Uptake Value (ΔSUV_max) between baseline and I-PET). Methods: Observational I-PET scans were performed after four cycles R(R)-CHOP14 (I-PET4) in the HOVON-84 randomized clinical trial (EudraCT 2006-005174-42), and centrally reviewed using DS (cut-off 4-5). Additionally, ΔSUV_max (prespecified cut-off 70%) and baseline MTV were measured. Multivariable hazard ratios (HR), positive (PPV), and negative predictive values (NPV) were obtained for 2-year PFS. Results: 513 I-PET4 scans were reviewed according to DS, and ΔSUV_max and baseline MTV were available for 367 and 296 patients. NPV of I-PET ranged between 82% and 86% for all PET response criteria. Univariate HR and PPV were optimal for ΔSUV_max (4·8 and 53%, respectively) compared to DS (3·1 and 38%, respectively). AaIPI and ΔSUV_max independently predicted 2-year PFS (HRs 3·2 and 5·0, respectively); adding MTV slightly improved this. Low/low-intermediate aaIPI combined with ΔSUV_max>70% (37% of patients) yielded a NPV of 93%, and the combination of high-intermediate/high aaIPI and ΔSUV_max≤70% a PPV of 65%. Conclusion: In this DLBCL study, I-PET after four cycles R(R)-CHOP14 added predictive value to aaIPI for 2-year PFS, and both were independent response biomarkers in a multivariable Cox model. We externally validated that ΔSUV_max outperformed Deauville score in 2-year PFS prediction.