Decitabine Can Improve the Efficacy of Second-Line Chemotherapy in Relapsed or Refractory Diffuse Llarge B Cell Lymphoma

Objective Diffuse large B cell lymphoma (DLBCL) is a commom and aggressive of non-Hodgkin lymphoma (NHL). The treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is a first-line treatment for diffuse large B-cell lymphoma,approximately 60-70% of patients can achieve cure, however, 30-40% of patients have disease that is either refractory to initial therapy or relapses after standard therapy.Decitabine is a nucleoside analogue and a hypomethylating agent,inhibits DNA methyltransferase ,which has previously been shown to have direct cytotoxic effects and/or affect cellular differentiation and apoptosis.Studies have found that after low-dose decitabinecanenhancethe chemosensitivity of various cancer cells.In addition,the reported that DNA methyltransferase inhibitors (DNMTI) could affect RR-DLBCL growth and overcome chemotherapy resistance.There is no standard second-line treatment for relapsed or refractory diffuse large B cell lymphoma (RR-DLBCL), and the prognosis is poor.This study prospectively observed the efficacy and safety of decitabine combined with second-line chemotherapy (R±DHAP) in the treatment of relapsed or refractory diffuse large B-cell lymphoma.

Methods This study was a prospective, one-arm, multi-center clinical trial (registration number: NCT03579082). Eligible petients were age 14 to 65 years whose survival were expected to be more than 3 months and histopathological diagnosis of diffuse large B-cell lymphoma,and had experienced relapse or did not achieve CR with a R-CHOP or R-CHOP-like regimen,which did not receive DHAP treatment before.Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2.Exclusion criteria included CNS involvement,There are any uncontrollable medical conditions (including uncontrolled diabetes, severe heart, lung, liver, kidney dysfunction),patients with severe infections,and patients who had received radiation therapy.15 patients with relapsed or refractory diffuse large B-cell lymphoma were enrolled, 13 patients were evaluated,including 6 males and 7 females with aged between 30-65 years old,the median age of the patients was 50 years old. One cycle every 21 days, decitabine 10 mg/d intravenous infusion d-5~-1; rituximab 375 mg/m², d0, ivgtt (rituximab can be used or not); cisplatin 100 mg/m² , divided into d1~3, ivgtt, cytarabine 2g /m², q12h, d2, ivgtt, dexamethasone 40mg, d1 ~ 4, ivgtt. The recent objective efficacy evaluation was evaluated using the 2017 NCCN guidelines, and the adverse events were ranked according to the NCI 5.0 evaluation criteria. The primary efficacy indicators were overall response rate (ORR) and time to progress (TTP) by imaging evaluation, and observation of adverse events.

Results A total of 15 patients were enrolled, 13 patients were evaluated, 1 complete response (CR), 6 partial response (PR), 3 stable disease (SD), The total effective rate (ORR ) was 53.8% and the median disease progression time (TTP) was 2.5 months.The main adverse event in this experiment was myelosuppression. According to clinical observation, the application of Pegylated Recombinant Human Granulocyte Colony Stimulating Factor (PEG-rhG-CSF) for Injection can significantly improve the myelosuppressive state.

Conclusion Decitabine can improve the efficacy of second-line chemotherapy in the relapsedand/or refractory diffuse large B-cell lymphoma, and the adverse reactions can be tolerated.

Key words decitabine relapsed or refractory diffuse large B-cell lymphoma efficacy