DA-EPOCH-R VS R-CHOP in Patients with Primary Mediastinal Large B-Cell Lymphoma: Results of Prospective Randomized Ukrainian Multicenter Study

Background

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinical, pathological and molecular subtype of diffuse large B-cell lymphoma (DLBCL), accounts approximately for up to 7% of all its cases and 2-4% of all non-Hodgkin's lymphomas. The standard 1st line treatment of PMBCL does not currently exist. The treatment approaches are still differing all over the world. A few retrospective analysis and lack of prospective data comparing the efficiency of R-CHOP and DA-EPOCH-R regimen, does not allow to establish the best front line treatment options.

Aims

In current study we aimed to compare the treatment efficacy and toxicity of DA-EPOCH-R and R-CHOP regimens in patients with PMBCL.

Patients and methods

In the study were included 69 patients with newly diagnosed PMBCL from six Ukrainian centers from Aug 2011 to Dec 2015. Median age was 27 years (range 17-45), 50 females (72,5%) and 19 males (27,5%). Early stages (I-II) had 68,1 % patients, 78,3% of patients had greatest size of the tumor mass in mediastinum more than 10 cm. Patients were randomized in two groups: DA-EPOCH-R (36 patients) or R-CHOP (33 patients). Primary endpoint: 5-year PFS. Secondary endpoints: ORR, CR rate, PR rate, 5-year OS and toxicity rate. Primary and post treatment assessment of disease included PET-CT or CT of the whole body. The treatment efficacy in both groups was evaluated according to Cheson criteria 1999, 2007 and Deauville criteria. Toxicity rates were evaluated according to NCI-CTC V.3.0. All patients received 6 cycles of R-chemo ± mediastinal radiation therapy (30-36 Gy).

Results

ORR and CR were significantly higher in R-da-EPOCH group: 97.7% vs 85% and 81.8 vs 50%, respectively. 2,3% of patients in R-da-EPOCH group and 15% in R-CHOP didn't respond tothe therapy. There were any relapses after completion of treatment in DA-EPOCH-R group. In the R-CHOP group relapses were observed in 15% of patients (mostly early relapses). All relapses happened within 24 months after treatment.

According to the analysis of long-term results, the 5-year PFS in the group of patients treated with DA-EPOCH-R was 90,9 % vs 64,1 % (p = 0.002) in the group of patients treated with R-CHOP. The 5-year OS in the DA-EPOCH-R group was 97.7% vs 73,8 % (p = 0.002), respectively. Neutropenia grade 3-4 was observed in 36,1% of cycles in R-da-EPOCH vs 20,6% in R-CHOP (p < 0.05) and FN in 15,7% vs 14,4% of cycles (p > 0.05). Anemia grade 3-4 was in 6,9% vs 8,7%, respectively(p > 0.05). Thrombocytopenia grade 3-4 was not observed. All cases of non-hematological toxicity were grade 1-2.ConclusionsThese results provide the confirmation by a multi-institutional study that DA-EPOCH-R regimen induses high durable remissions in PMBCL and more effective than traditional R-CHOP. Toxicity was tolerable in both groups, but the rate of neutropenia grade 3-4 was higher, but manageable in the group of R-da-EPOCH than in the group of R-CHOP.