PF472 VERY LATE REALAPSES (VLR) ≥5 YEARS AFTER INITIAL TREATMENT WITH CHEMOTHERAPY±RADIOTHERAPY (CT±RT) IN HODGKIN LYMPHOMA (HL): A JOIN STUDY ON TREATMENT STRATEGIES AND PROGNOSTIC FACTORS FOR THE OUTCOME
Authors: Vassilakopoulos T. , Liaskas A. , Rizzuto G. , Angelopoulou M. , Giatra H. , Kontopidou F. , Dimopoulou M. , Musseti A. , Siakantari M. , Asimakopoulos I. , Arapaki M. , Triantafyllou F. , Chatzidimitriou C. , Yannikos T. , Korkolopoulou P. , Cabras A. , Rassidakis G. , Dimou M. , Variami E. , Panagiotidis P. , Corradini P. , Bakiri M. , Karmiris T. , Konstantopoulos K. , Pangalis G. , Viviani S. 
Published: December 2023

Background:

Risk‐adapted treatment strategies have improved the long‐term outcome of patients with Hodgkin Lymphoma (HL) and traditionally the disease is considered cured after a 5‐year continuous first complete remission (CR1). However, our initial report and the recent large GHSG study have demonstrated that VLRs, occurring ≥5 years after initial treatment initiation, are a non‐negligible event. Due to the rarity of these events very few data exist describing the outcome of VLRs after CT ± RT while there is no study focusing on potential prognostic factors

Aims:

This study aimed to describe the treatment strategies adopted for patients with VLRs as well as their outcome and prognostic factors for Freedom From Second Progression (FF2P) and Overall Survival after failure (O2S)

Methods:

Cases were identified retrospectively from the databases of the 5 participating centers (4 referral centers in Greece and 1 in Northern Italy). Patients were eligible if they had remained in CR1 for ≥5 years after initial CT ± RT and had experienced VLR. Study endpoints were the estimation of FF2P and O2S and the identification of relevant prognostic factors

Results:

A total of 103 patients were identified. 69% were males, 18% were ≥65 years old at relapse, 24% had relapsed >15 years after the initial diagnosis, 38% had B‐symptoms, 25% extranodal disease and 30% anemia at relapse. The initial histologic subtype was nodular lymphocyte predominant in 13% of the cases, lymphocyte rich classical in 3%, nodular sclerosis (NS) in 43% and mixed cellularity in 40%. Reinduction with the same regimen was given in 24% of the cases, 6 patients (6%) received salvage RT only and 26% received salvage chemotherapy with the intention to proceed to autologous transplant (ASCT; 30% for patients <65 years). The 5‐ and 10‐year FF2P was 55% and 50%, while the O2S was 78% and 55% respectively. Among 37 deaths, 21 were due to HL and 1 due to toxicity of salvage therapy, while 11 were purely attributed to 2nd malignancies and 4 to unrelated causes. Patients with and non‐nodular sclerosing classical HL histologic subtype seemed to have worse FF2P but this was not an independent prognostic factor. Reinduction with the same regimen did not significantly affect FF2P and O2S; 5/6 patients selected for salvage RT only had long‐term remission. Intention to proceed to ASCT was associated with numerically higher FF2P and O2S in patients <65 years old, but the differences did not reach significance [5‐year FF2P 82% vs 56% but 10‐year rates 59% vs 56% (p = 0.57) and 10‐year O2S 84% vs 59%, (p = 0.19)]. In multivariate analysis only anemia at relapse was independent predictor of FF2P (p = 0.025) but age ≥65 (p = 0.064) and B‐symptoms at relapse (p = 0.073) entered the model with borderline significance. Both anemia and age ≥65 years at relapse were independent adverse prognostic factors for O2S (p = 0.042 and p < 0.001 respectively). The presence of either anemia and/or age ≥65 years at relapse identified a subgroup comprising 41% of the whole patient population who had highly compromised 10‐year FF2P and O2S (65% vs 28% and 66% vs 35% respectively for patients, p < 0.001 for both)

Summary/Conclusion:

The prognosis of VLRs after CT±RT for HL does not appear favorable. However, a considerable proportion of patients relapse at advanced age and also, a non‐negligible number of patients succumb to 2nd malignancies and unrelated conditions. Salvage RT may cure a small proportion of eligible patients, while ASCT should be considered despite the long duration of the initial remission. Advanced age and anemia at relapse were the most important prognostic factors in our study