ABCL-070 Multicenter Randomized Controlled (Comparative) Open Prospective Study to Evaluate the Efficacy of the R-DA-EPOCH-21 and R-mNHL-BFM-90 ± Autologous Hematopoietic Stem Cell Transplantation Programs in Untreated Patients With Diffuse B-Cell Large Cell Lymphoma With Signs of Poor Prognosis - DLBCL-2015 Protocol

Abstract

Short-pulse NHL-BFM-90 chemotherapy is highly effective in pediatric aggressive B-cell lymphomas. We modified R3 arm of NHL-BFM-90 program (R-mNHL-BFM-90) for adults under 60 years with high-risk de novo DLBCL and conducted the randomized study compared with R-DA-EPOCH-21 chemotherapy. To evaluate efficacy and toxicity in de novo adult DLBCL patients with 2 or more signs of poor prognosis. Treatment protocol was registered as NCT02842931 at www. gov. Inclusion criteria were newly diagnosed DLBCL, not otherwise specified (NOS), according to WHO, 2008 and 2017 criteria, intermediate and high age-adjusted International Prognostic Index (aaIPI) risk, age 18-60. Response was corresponded by Lugano 2014 criteria. The study design intended randomization for four parallel arms: -6-cycle R-DA-EPOCH-21; - 6-cycle R-DA-EPOCH-21 plus auto-HSCT; - 6-cycle (A-B-A-B-A-B) R-mNHL-BFM-90; - 6-cycle R-mNHL-BFM-90 plus auto-HSCT. If CR wasn't achieved after treatment in every arm additionally 2-cycle R-DHAP chemotherapy were completed before auto-HSCT. A total of 140 patients from 13 Russian clinics were included from February 2015 to June 2021. Randomization was done according "intention-to-treat" as follows: R-DA-EPOCH-21 (35 patients); R-DA-EPOCH-21+auto-HSCT (30 patients); R-mNHL-BFM-90 (37 patients); R-mNHL-BFM-90+auto-HSCT (38 patients). First-step analysis was carried out for 130 patients according "intention-to-treat." In all cases, the final diagnosis was assessed as indolent lymphoma transformation into DLBCL or other "non-DLBCL" lymphomas. Second-step analysis was performed for 116 "proved" de novo DLBCL patients. Evaluation of comparative efficacy was carried out in R-DA-EPOCH-21±auto-HSCT and R-mNHL-BFM-90±auto-HSCT cohorts. Hematological/non-hematological toxicity was acceptable in all groups. However, neutropenic fever and grade 3-4 thrombocytopenia differed statistically significantly (χ2 test, p<0.05) between R-DA-EPOCH-21 and R-mNHL-BFM-90 arms. The value of auto-HSCT will be determined later. De novo DLBCL NOS is potentially a curable disease with no relapses. R-mNHL-BFM-90 program is highly effective in de novo DLBCL NOS adult patients. R-mNHL-BFM-90 therapy toxicity is acceptable. The estimated CR duration probability within 10 months after treatment completion in the high-risk group is 100% in R-mNHL-BFM-90 group compared to 57% in R-DA-EPOCH group (χ2 test, p=0.0047).