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

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-α, IFN-γ) 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 ≤2) following BV. 19 pts (18 with Deauville 2 response and 1 with Deauville 3 response after BV) proceeded directly to ASCT. Among the other 46 pts, 1 was lost to follow-up; 45 received augICE chemotherapy of which 31 (69%) achieved CR. Overall, 49 (75%) of 65 pts achieved complete response and 64 pts proceeded to ASCT. 3-year overall survival and EFS were 95% and 82%. Factors predictive for EFS by univariate analysis included age over 45 years (p = 0.016), refractory disease (p = 0.033), B-symptoms (p = 0.032), advanced stage at relapse (p = 0.011), as well as baseline MTV, TARC, and TLG (all p < 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). Keywords: brentuximab vedotin; Hodgkin lymphoma (HL); positron emission tomography (PET).