Survival Patterns of Non-Randomized Patients in the IELSG37 Study: Deauville Score 4 Is Not Necessarily Associated with Poor Outcome in Primary Mediastinal Lymphoma

Background:Primary mediastinal B-cell lymphoma (PMBCL) is clinically and biologically distinct from other types of aggressive lymphoma, it is characterized by a bulky mediastinal mass and most commonly occurs in women between 30 and 40 years of age. Although consolidation radiotherapy (RT) has yielded extremely positive outcomes in PMBCL, it carries a higher risk of long-term complications. Consequently, there has been an ongoing debate regarding the necessity of RT in patients responding to frontline immunochemotherapy. Methods:In the IELSG37 study, PMBCL 530 patients were treated with rituximab- and doxorubicin-containing regimens; 98% had stage I-II. Their response was assessed by positron emission computed tomography (PET/CT); 268 achieved a complete metabolic remission (CMR) defined as Deauville score (DS) 1 to 3 according to the Lugano classification and were randomly allocated to observation or mediastinal RT. The primary analysis [Zucca et al. J Clin Oncol 2023; 41 (suppl 17): abs. LBA7505] has shown that patients in CMR can safely forgo RT. The 3-year overall survival (OS) rate was 99% irrespective of irradiation. RT provided only minimal benefit on progression-free survival (PFS), which was over 96% at 3 years in both arms. Here we present the outcome of the 262 patients who were not randomized and were managed according to the preference of their treating physician. Results:Median follow-up was 64 months (interquartile range [IQR], 49-69). Besides 230 patients failing frontline treatment (174 DS4 and 56 DS5), the non-randomized cohort also included 1 patient with DS2 (who refused randomization and received RT) and 31 patients with DS3 who were initially considered as partial responders before a protocol amendment that changed the definition of CMR from DS 1-2 to DS 1-3. Among these non-randomized patients with DS3, 27 had RT consolidation, 1 was only observed, 2 had salvage chemotherapy ± RT, and 1 had missing data due to consent withdrawal; their 3-year PFS was very close to the one of the randomized patients with DS3 (90 vs 92%, p=0.99). In the DS4 group, 12 patients were observed, 149 had only RT, and 13 had second-line chemotherapy, with (12) or without (1) autologous stem cell rescue, 8 of 13 also had RT. Among the patients with DS5, only 2 were observed, 32 had only RT, and 22 had second-line chemotherapy, with (15) or without (7) autologous stem cell rescue; 12 of them also had RT. The outcome of patients with DS4 was overlapping the one