Prognostic Significance of PET Imaging in Relapsed or Refractory Classical Hodgkin Lymphoma Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation.
Authors: Smeltzer Jacob , Cashen Amanda F , Zhang Qin , Abboud Camille N. , DiPersio John F. , Stockerl-Goldstein Keith , Uy Geoffrey L. , Vij Ravi , Westervelt Peter , Bartlett Nancy L , Fehniger Todd A 
Published: October 2019

Abstract
Abstract 3417
Poster Board III-305
Standard treatment for classical Hodgkin lymphoma (cHL) that has relapsed or is refractory (rel/ref) after front-line therapy consists of standard dose salvage chemotherapy followed by high dose chemotherapy with autologous stem cell transplantation (ASCT). However, the long-term disease free survival in rel/ref cHL patients utilizing this approach is heterogeneous. A number of prognostic factors have been identified retrospectively, with the goal of defining patients that achieve long term remission with ASCT and those with a high risk of relapse. We examined 106 rel/ref cHL patients that underwent ASCT at Washington University from January 2001 to December 2007 with comparable salvage and ASCT therapy. We focused on the 77 patients that had a PET or PET/CT scan pre-ASCT following 2-4 cycles of standard salvage therapy. PET imaging reports were reviewed and interpreted as negative (42%) or positive (58%), with a positive PET conservatively defined as any abnormal residual FDG uptake at a site of prior disease. Median age was 34 (18-70) years with 39% females, median follow-up from ASCT was 38 (range 0.5-85) months. Front-line therapy consisted of ABVD (82%), Stanford V (7%), MOPP/ABV (4%), RT only (3%), or other (4%). High dose conditioning consisted of BEAM (99%) or BEAC (1%). At the time of relapse, stage was I (7%), II (44%), III (24%), or IV (25%). Prognostic factors originally identified by Moskowitz et al. at the time of relapse were 1st remission duration < 1 year (65%), presence of B symptoms (36%), or presence of extranodal disease (27%); these yielded scores at the time of relapse of 0-1 (62%), 2 (28%), or 3 (10%). The German relapsed Hodgkin prognostic score factors (rHPS; 1st remission duration ≤ 1 year, stage III/IV at relapse, anemia at relapse) were available in 75 patients, resulting in scores of 0 (16%), 1 (47%), 2 (28%), or 3 (9%). The modified 4 factor IPS score at relapse reported by Bierman et al. (albumin < 4 g/dL, age ≥ 45 years, anemia, lymphocytopenia) in the 65 patients with these data available was 0 (52%), 1 (35%), 2 (11%), 3-4 (2%). The response to salvage therapy based on PET and CT report when available was CR (42%), PR (46%), SD (5%), or PD (7%). The 2 year event free survival (EFS) and overall survival (OS) for 77 patients with a pre-ASCT PET was 63% and 87% respectively, and the 5 year EFS and OS was 52% and 78% respectively. In univariate analysis positive PET imaging post-salvage therapy was a significant adverse factor on EFS (P=0.005), with a non-significant trend for OS (P=0.133). The 2 year EFS and OS for PET positive patients was 47% and 81%, and the 2 year EFS and OS for PET negative patients was 87% and 100% (see figure). Multivariate analysis indicated that the PET imaging result (P=0.007, HR 3.7, 95%CI 1.43-9.39) and the Moskowitz score (P=0.04, HR 1.84, 95%CI 1.03-3.30) were significantly associated with EFS, while the modified 4 factor IPS (P=0.43) and the rHPS (P=0.44) were not significant. We conclude that PET imaging results, even with a conservative interpretation that any residual abnormal uptake is positive, facilitate prediction of EFS following standard salvage chemotherapy and ASCT in rel/ref cHL patients. A substantial number of PET positive patients by the criteria used in this study were successfully treated with salvage chemotherapy and ASCT. Future studies are warranted to define PET imaging as a prognostic factor prospectively in rel/ref cHL, and uniform standards to assess PET imaging as positive or negative are needed.

Disclosures
DiPersio: Genzyme: Honoraria.