Novel Targeted Agents In Combination With R-ice (r-ice-x) Based On Genotyping In Relapsed/refractory Dlbcl
Topic: Aggressive Non-Hodgkin lymphoma — Clinical
Background:
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma,which is characterized by high heterogeneity, rapid progression and poor prognosis. 30%-40% of the patientsare relapsed or refractory to R-CHOP treatment, and only about 40% patients get benefits from second-lineregimens including R-ICE. The outcomes of these relapsed/refractory (R/R) DLBCL remain to be improved.Aims:This prospective, single-arm study aims to investigate the efficacy and safety of a new targeted agent incombination with R-ICE (R-ICE-X) based on different molecular subtypes in R/R DLBCL patients, providing anew treatment for improving clinical efficacy in DLBCL patients with poor prognosis.
Methods:In this study, patients with R/R DLBCL aged 18–75 years were enrolled. All patients were assigned and stratifiedby genetic subtypes and received different targeted agents combined with R-ICE. The efficacy was evaluatedafter 3 courses of R-ICE-X (every 21 days). Patients with complete remission or partial remission (CR/PR) weresubsequently treated with autologous hematopoietic stem cell transplantation (ASCT) or 3 courses of R-ICE-Xconsolidation and lenalidomide maintenance for up to 12 months. The primary endpoint was the overallresponse rate (ORR), and the secondary endpoints were the 2-year progression-free survival (PFS) rate, 2-yearoverall survival (OS) rate, and safety evaluation. This trial is registered with ClinicalTrials.gov, NCT05348213.
Results:At the time of data cut off, a total of 76 patients were enrolled, with a median age of 61 (20–75) years. Among71 patients who completed treatment, the end of induction CR rate was 59.2%, and ORR was 78.9%. In thepatients with R-ICE-zanubrutinib group (n=34), the ORR was 78.8%, with 18 patients (18/33, 54.6%) achievedCR and 8 patients (8/33, 24.2%) achieved PR. The 1-year PFS rate and OS rate were 70.2% and 86.5%,respectively. In the patients with lenalidomide combined with R-ICE (n=30), 17 patients (17/30, 56.7%)achieved CR, 6 (6/30, 20.0%) patients achieved PR, and the ORR was 76.7%. The 1-year PFS and OS rates were84.0% and 100.0%, respectively. 5 patients (5/8, 62.5%) with decitabine plus R-ICE achieved CR. 2 patientsreceived R-ICE-chidamide and got CR as well. Only one patient in R-ICE-tofacitinib considered other clinicalstudies due to poor treatment efficacy. Furthermore, we found the proportion of SOCS1 mutation wasincreased in patients with poor response to R-ICE-X regimen. In univariate analysis, we also revealed that CD70,SOCS1 and TMSB4X mutations indicated poor survival outcomes. Subsequent analyses of poor prognosisgenes in each treatment group will be performed.
Summary/Conclusion:Novel targeted agents in combination with R-ICE (R-ICE-X) regimen was well tolerated and efficacy in R/RDLBCL patients, being a promising bridging regimen for ASCT, especially R-ICE-zanubrutinib and R-ICE-lenalidomide therapy. The study is ongoing and further results will be continuously released.