BASELINE METABOLIC TUMOR VOLUME IS AN INDEPENDENT PROGNOSTIC FACTOR FOR RELAPSED AND REFRACTORY HODGKIN LYMPHOMA PATIENTS RECEIVING PET‐ADAPTED SALVAGE THERAPY WITH BRENTUXIMAB VEDOTIN AND AUGMENTED ICE

Abstract

Introduction: Identification of prognostic factors for patients (pts) with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) is essential for optimizing therapy by designing risk‐adapted treatment strategies. In our phase II study of PET‐adapted salvage therapy (ST) with brentuximab vedotin (BV) and augmented ICE (augICE) we assessed clinical factors, quantitative PET assessments, and serum cytokine/ chemokine values as potential prognostic factors predictive of event free survival (EFS). Methods: Transplant eligible pts with rel/ref HL following 1 line of therapy were eligible. Pts received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV (1.2 mg/kg days 1, 8, 15 of 28 day cycles); PET‐negative pts proceeded directly to autologous stem cell transplant (ASCT) while PET‐positive pts received augICE before ASCT. Serum cytokines and chemokines (TARC, IL‐6, IL‐10, TNF‐alpha, IFN‐gamma) were measured at baseline and after BV. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured at baseline, after BV and after augICE. Results: 65 pts enrolled (45 cohort 1, 20 cohort 2), including 34 (52%) females, 29 (45%) with advanced stage disease, 34 (52%) with refractory disease (lack of CR after front‐line therapy), 10 (15%) with B symptoms, 24 (37%) with extranodal disease, and 16 (25%) with bulk (any mass > 5 cm). Overall, 18 of 65 (28%) pts achieved complete response (defined as Deauville < 0.001). Factors that remained prognostic by multivariate analysis were MTV (p < 0.001, HR 54, 95% CI 9‐319) and refractory disease (p = 0.001, HR 82, 95% CI 6.1‐1107). The optimal cut‐off for baseline MTV, determined by a grid search of log‐rank test p values, was 109.5 cm3. Using this cutoff, the 3‐year EFS for pts with low (n = 48) and high (n = 12) MTV was 92% and 27% respectively (p < 0.001) (Figure). Conclusion: In this phase II study of PET‐adapted ST with BV and augICE for rel/ref HL, baseline MTV and refractory disease were independent prognostic factors for EFS. Additional studies are needed to confirm the prognostic significance and optimal cutoff for MTV in rel/ref disease. Future studies should optimize efficacy and tolerability of ST by stratifying pts according to risk factors such as baseline MTV. (Figure Presented).