Treatment options, responses and outcome of 1220 classic Hodgkin lymphoma patients included in realysa, a prospective multicentric lysa cohort

Abstract Background: Classic Hodgkin lymphoma (cHL) therapies are progressing with different first-line chemotherapy regimens (CT), possibly in combination with monoclonal antibody, PET monitoring during treatment and limitation of consolidation radiotherapy (RT). It is important to analyze how these modifications are implemented in clinical practice given the current complexity of the therapeutic landscape in cHL. Methods: REal world dAta in LYmphoma and Survival in Adults (REALYSA) is a prospective non-interventional multicentric cohort (NCT03869619) including 6015 patients newly diagnosed with lymphoma in France between Nov 2018 and Oct 2023. In this study, we analyzed 1220 cHL patients treated in first-line therapy who participated to REALYSA. Objectives were to describe therapeutic strategy according to age (<60 and ≥ 60 years old), risk-factors (early-stage I/II with 0-2 and ≥ 3 nodal areas involved, infra-diaphragmatic disease, advanced stage III/IV and IIB with risk-factors), treatment response, outcome with event-free survival (EFS) and overall survival (OS) with the evaluation of some prognostic factors for EFS using a “flexible” Cox model, with penalised splines for continuous covariates. In this multivariable regression model, stage and bulk were analyzed as categorical covariates and age, absolute lymphocyte count (ALC) and hemoglobin levels as continuous covariates through penalised splines. Results: 1220 cHL patients were included in REALYSA in 35 French centers. The median age was 33.8 years (Min 18 ; Max 89) with 158 patients ≥ 60 years (13%). 94% of patients had performance status (PS) 0-1, 49% presented B-symptoms, 21% extra-nodal involvement >1 and 16% bulky disease ≥10cm. PET was performed for 1204 patients (99%) at initial staging, 1103 (90%) after 2 cycles (PET2) and 1031 (85%) at end of treatment (EOT). Staging were as follows: infradiaphragmatic disease (n=38, 3%), I/II with 0-2 nodal areas (n=178, 14%), I/II with ≥ 3 nodal areas (n=338, 28%), IIB with risk factors (n=36, 3%), III/IV (n=630, 52%). Median of hemoglobin, leukocytes, ALC and albumin levels were 12.5 g/dl, 9.6 G/L, 1.4 G/L, 37 g/l, respectively. Missing data for key variables were rare: <1% for PS, hemoglobin, leukocytes, ALC, 2% for bulk and 25% for albumin. For older patients, 52% received ABVD, 6% BV-AVD, 18% PVAB, 13% PVAG, 10% non-anthracycline-based regimen, 1% other anthracycline-based regimens. Patients <60 years (n=1062) received upfront eBEACOPP (44%), ABVD (43%), OEPA (4%), eBEACOPDac (7%), BRECADD (1%), BV-AVD (1%) and <1% other anthracycline-based and non-anthracycline-based regimens. For advanced stage (IIB with risk factors, III/IV), 75% of younger patients were treated with intensive chemotherapy (eBEACOPP, eBEACOPDac, BRECADD), 87% of them with dose de-escalation strategy based on PET2 results. Consolidation RT was used for 51% and 71% of younger and older patients with early stage, respectively. EOT complete responses were documented for 73% and 92% of patients ≥ 60 and < 60 years, respectively. With a median of follow-up of 31 months (95%CI, 30-32), 3-year EFS rates were 84%, 87% and 65% for whole cohort, patients <60 and ≥ 60 years, respectively (P<0.001 between the two age groups). For younger patients, 3-year EFS rates were 94%, 94%, 88%, 86% and 84% for infradiaphragmatic disease, I/II with 0-2 nodal areas, I/II with ≥ 3 nodal areas, IIB with risk factors and III/IV stage, respectively. For older patients, 3-year EFS rates were 85% and 56% for I/II and III/IV stage, respectively. At last follow-up, 43 patients died (3.5%) corresponding to 3-year OS rates of 96%, 99% and 78% for whole cohort, younger and older patients, respectively. Prognostic analyses using flexible Cox model showed that hemoglobin level (P=0.025) with a trend for ALC (P=0.095) predicted EFS for early stage. For advanced stage, age (P<0.001) predicted EFS with a trend for hemoglobin level (P=0.071). Conclusions: REALYSA cohort provides high quality real world data for cHL patients. Younger patients with advanced stage were mainly treated with intensive regimens with dose de-escalation PET adapted strategy. For early stage, we observed a reduction of consolidation RT used. Outcome data confirmed the poorer prognosis of older patients. This cohort is a source of a multitude of different applications including innovative comparisons with most recent results using immunochemotherapy regimens.