Radiotherapy in Young, High-Risk Patients with Aggressive B-cell Lymphoma: Long-Term Results from the Open-Label, Randomized, Phase 3 R-MegaCHOEP Trial

Abstract

The role of consolidative radiotherapy (RT) for young (< 60 years), high-risk patients with aggressive B-cell lymphoma is discussed. The R-MegaCHOEP trial investigated the use of high-dose chemotherapy and rituximab with subsequent autologous stem cell transplantation compared to conventional R-CHOEP immunochemotherapy for patients up to 60 years1,2. Despite no prognostic difference between treatment arms even after 10-year follow-up, excellent long-term results were achieved. The presented work represents a detailed RT-analysis providing long-term data on efficacy and side-effects. The 10-year follow-up dataset of the R-MegaCHOEP trial with a median follow-up of 81.1 months (range 0.6-175.9 months) was used for this analysis. Indications for consolidative RT were extralymphatic involvement or bulky disease (maximum diameter ≥ 7.5 cm). Additionally, RT could be administered because of insufficient response at end of therapy as evaluated by CT scan. Overall, 261 patients were analyzed, 120 of whom underwent RT. Patients with RT were predominantly male (65.8 %), had an age-adjusted IPI of 2 (75 %), an elevated LDH (96.7 %) and showed an ECOG-Score of 0-1 (65 %). Bulky disease was present in 103/120 patients in the RT-arm with a bulk size of 7.5-20.0 cm (median: 11 cm) and was located predominantly in the mediastinal (44), paraaortal (17) and mesenteric (13) regions. The most frequently irradiated regions were the mediastinal (50), paraaortic (27) and mesenteric (15) regions. Median RT dose was 36 Gray in median fractions of 1.8 Gray. Toxicities were generally mild to moderate with 24 and 8 grade 3 and 4 toxicities reported during RT. During long-term follow-up, 23 secondary malignancies occurred, with RT being no significant contributing risk factor (p = 0.188). Analysis of the overall study population showed that patients with RT had an improved event-free survival (EFS; 63.9 % vs. 46.0 %; p<0.001) and progression-free survival (PFS; 67.2 % vs. 54.1 %; p = 0.025) but not overall survival (OS; 72.8 % vs. 65.9 %; p = 0.132) in comparison to non-irradiated patients after 10 years. Considering only those patients with RT after a complete remission/unconfirmed complete remission after systemic therapy, a significantly improved EFS (66.4 % vs. 46.0 %; p = 0.006), but not PFS and OS, was shown (PFS: p = 0.054; OS: p = 0.222). For patients with bulky disease, RT resulted in a significantly better outcome (10-year EFS: 64.4 % vs. 34.5 %; p<0.001; 10-year PFS: 68.3 % vs. 47.4 %; p = 0.003; 10-year OS: 71.5 % vs. 59.4 %; p = 0.011), when compared to patients without RT. For patients with extralymphatic involvement, RT improved EFS (10-year EFS: 61.7 % vs. 51.1 %; p = 0.017), but not PFS or OS (PFS: p = 0.068; OS: p = 0.305). RT improved outcome in young, high-risk patients with aggressive B-cell lymphoma and bulky disease. NCT00129090. 1 Lancet Oncol 2012;13(12):1250-1259. 2 Lancet Haematol 2021;8(4):e267-e277.