REAL‐LIFE EXPERIENCE WITH RITUXIMAB‐DOSE‐ADJUSTED EPOCH (R‐da‐EPOCH) IN PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA (PMLBCL): A MULTINATIONAL ANALYSIS OF 274 PATIENTS

Background: Real-life studies of moderate size have shown satisfactory but less impressive results compared with the original R-da-EPOCH publication for PMLBCL. However, large studies are needed efficacy and toxicity of R-da-EPOCH, the use of radiotherapy (RT) and significance of the compliance with the strict dose escalation strategy of the protocol. Aim: To assess the clinical outcomes after R-da-EPOCH, the use of RT and protocol compliance in a multinational real-life setting. Patients and Methods: 274 patients (pts) were enrolled from 18 Greek, Israeli, Turkish, Saudi, Cypriot and Maltese centers (n = 143, 66, 34, 22, 5 and 4 pts respectively). Consolidative RT was given at the treating physician’s discretion and was highly affected by PET/CT results. Results: The median age of the pts was 33 years (16–63), 62% were females, 38% had B-symptoms, 33% extranodal involvement (E or stage IV), 18% PS ≥ 2, 83% elevated LDH (34% highly elevated ≥2x normal). RT was spared in the overwhelming majority of responders. The 5-year Freedom From Progression (FFP) was 85%. However, 5 pts developed therapy-related (t-)AML at 10.5–24 months from treatment initiation, while in 1st remission, and one Hodgkin lymphoma. The 5-year overall survival (OS) was 91% with 20 disease-related deaths (1 toxic). Protocol violations were common (54% of 245 patients with available data so far), mainly consisting of insufficient dose escalation despite the absence of prohibitive toxicity. Among 258 pts with available data, 60% reached level ≥3 and 30% ≥4 (73% and 44% among those with strict protocol adherence). The 5-year FFP was 89% versus 83% for pts with strict protocol adherence or not (p = 0.19); 5-year OS was not also different (91% vs. 92%, p = 0.74). FFP and OS did not differ according to the final level reached (≥3 or ≥4). A more detailed analysis of outcome according to the degree of protocol violations is currently ongoing. Pts with both risk factors according to the prognostic systems including any extranodal involvement and highly elevated LDH (≥2x) or bulk had inferior outcomes but still better than those achieved by R-CHOP in high-risk pts. Conclusions/Discussion: In the largest series reported so far for R-da-EPOCH in PMLBCL, FFP appeared somewhat but not impressively better than the expected with R-CHOP, but this was achieved with the safe omission of RT was in >85% of responders. OS was >90%. The appearance of 5 cases of t-AML among 274 pts is worrisome. Significant dose-escalation violations were recorded in the real-life; their impact on outcomes appears to be modest and is further evaluated. A final analysis on 290–300 pts will be presented at the Meeting. Keyword: Aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.