Treatment strategies and prognostic factors for the outcome of patients with hodgkin lymphoma experiencing very late relapses after chemotherapy ± radiotherapy

Background: Despite the excellent long-term outcome of patients with Hodgkin Lymphoma (HL), some cases will be primary refractory or will eventually relapse, mainly within the first 2 years from diagnosis. Patients with sustained complete remission (CR) for ≥5 years are generally considered “cured”. However, Very Late Relapses (VLRs), occurring ≥5 years after treatment initiation, are a non-negligible event and possibly comprise a distinct entity with unique characteristics. Aim: The aim of the current study is to describe the treatment strategies adopted for patients with VLRs as well as their outcome and relevant prognostic factors. Patients/Methods: Patients with HL who experienced VLRs ≥5 years after treatment Initiation with chemotherapy ± radiotherapy (CT±RT), were identified retrospectively from the databases of 8 referral centers. Statistical endpoints were the estimation of time to second failure (TT2F) and Overall Survival after failure (O2S). Results: 145 patients with VLRs were identified. The median age was 49 years (19–82), 69% were males and 18% were ≥65 years old. In 23% of the patients, relapse occurred >15 years after the initial diagnosis. Reinduction with the same regimen was given in 24% of the cases, and 26% were indented to proceeded to high-dose therapy and autologous stem cell transplantation (HDT/ASCT). The 5- and 10-year TT2F were 57% and 53% and the 10-year and 15-year O2S were 59% and 46% respectively. Among 52 deaths, only 28 were disease-related whereas others were attributed to secondary malignancies or unrelated causes. Re-induction with the same regimen did not significantly affect TTF2 and O2S. Despite the numerical difference regarding 5-year FF2P for patients <65 years old who received HDT/ASCT, this was not statistical significant and there was no difference at 10 years. In multivariate analysis B-symptoms, extranodal disease, age ≥65 at relapse, and occurrence of relapse <15 years from diagnosis were independent adverse prognostic factors for TT2F (p = 0.03, 0.003, 0.005 and 0.006 respectively). Anemia, age ≥ 65 and extranodal disease at relapse were also associated with impaired O2S (p = 0.02, <0.001 and 0.044 respectively). We assigned one point to each of the aforementioned unfavorable factors and constructed prognostic scores. Patients combining 2–3 adverse characteristics had significantly compromised outcomes. None of the patients survived at 10-years with the 10-year disease-free-survival being only 36%. Conclusion: The prognosis of VLRs does not appear very favorable, however a considerable proportion of patients were ≥65 years old at the time of relapse when treatment options are limited and also, many patients succumb to disease-unrelated causes. Treatment approaches were heterogenous. In our study B-symptoms, extranodal disease and age ≥65 at relapse were the most important prognostic factors for the outcome of patients with VLRs. Keyword: Hodgkin lymphoma No conflicts of interests pertinent to the abstract.