Application Of Bendamustine-containing Therapy In Indolent B-Cell Lymphoma And Chronic Lymphocytic Leukemia

Objective:To compare the efficacy and safety of therapeutic regimens containing bendamustine as BR regimen（bendamustine plus rituximab）with R-CHOP（rituximab+cyclophosphamide+doxorubicin+vincristine+prednisone）in both indolent non-Hodgkin’s lymphoma（iNHL）and chronic lymphocytic leukemia（CLL）respectively.Thus providing the optimal choice for the clinical treatment of iNHL and CLL.Methods:1.The clinical data of hospitalized patients with indolent B-NHL and CLL who treated in Department of Hematology,First Affiliated Hospital of Anhui Medical University from June 2018 to July 2021 were collected.The 68 patients were separated into two groups on the basis of distinct antineoplastic protocols.The group containing bendamustine regimen（BR regimen）was called the experimental group（n=40）and the group without bendamustine applied（R-CHOP/Ibrutinib）was the control group（n=28）.The efficacy was evaluated every 2 to 3 treatment cycles.The efficacy evaluation criteria were based on the Lugano efficacy evaluation criteria for non-Hodgkin’s lymphoma.The primary evaluation indicator was the overall response rate（ORR）.Safety evaluation will be performed before and after each treatment cycle.Safety assessment will refer to National Cancer Institute Common Terminology Criteria for Adverse Events 5.0（NCI-CTCAE 5.0）.The efficacy and adverse events of patients after treatment with different regimens were compared.2.To analyze the clinical data of patients,Analysis was performed according to different disease classifications and clinical characteristics of patients,compare the short-term efficacy and safety of bendamustine-containing chemotherapy regimens in patients with different clinical characteristics,to reveal the indications for the clinical use of bendamustine.Results:1.54 Of the 68 patients received a systematic response assessment for efficacy,the overall response rate（ORR）was 74.1%in the group treated with BR,which was similar to the ORR（63.0%）in R-CHOP（P=0.38）,and disease control rate（DCR）was 88.9%and 100%,respectively（P=0.08）.2.Adverse reactions occurred in 46 of 68 patients,and the main adverse event（AE）was hematological toxicity（42/68）,it is mostly mild（32/42）.The incidence of myelosuppression in BR group was higher than that in control group（77.8%vs 51.9%,P=0.03）,and the grade 3-4 myelosuppression incidence was also higher（25%）.Other adverse reactions included infection（11 cases）,rash（6 cases）,neuropathy（3 cases）,joint pain（3 cases）and so on.No significant variation was found in occurrence rate between the two groups（P>0.05）.3.Subgroup analysis in INHL patients disclosed that the ORR and AE rates were similar between patients with different age,gender,risk and bone marrow involvement treated with BR and RCHOP regimens,respectively（P>0.05）.However,The incidence of adverse reactions in patients with MZL treated with the BR regimen was significantly higher than that with the RCHOP regimen（100%vs 42.9%,P<0.05）.4.Subgroup analysis in CLL patients uncovered that the ORR of the BR group was higher than ibrutinib group in elderly CLL patients aged>60 years（100%vs 20%,P=0.04）,and its safety was not inferior to ibrutinib group（P>0.05）;the effective rate of the BR regimen in relapsed and refractory CLL patients was also superior to ibrutinib group（100%vs 0%,P=0.008）,while no advantages was observed in the efficacy of the BR regimen in patients aged<60 years and newly diagnosed CLL.Patients in the early stage of disease and low-risk groups of CLL disease had a higher incidence of adverse reactions using the BR regimen than that using ibrutinib.5.Genetic mutation testing was performed in 23 CLL patients,and 78.3%of patients had one or more molecular genetic abnormalities like IGH monoclonal rearrangement,chromosome 13（D13S319 and RBI gene deletion）,and trisomy of chromosome 12.ORR In patients with genetic mutations which suggest a poor prognosis was generally lower than that in people without genetic mutations.BR and Ibrutinib monotherapy regimens had similar ORR and safety in patients with genetic mutations,while patients with p53 gene deletion had a significantly higher AE rate with BR regimen compared with Ibrutinib（P=0.025）.Conclusion:1.This study shows that BR regimen is an effective and tolerable treatment choice for indolent B-NHL.2.BR regimen treatment is preferred in elderly（≥60 years）CLL patients,while no benefit of BR was observed in CLL patients aged<60 years.3.Ibrutinib regimen is preferred in CLL patients with newly diagnosed,while relapsed and refractory CLL patients may benefit more with BR regimen.4.CLL patients with del17p give priority to ibrutinib regimen,however,whether BR regimen is preferred for CLL patients in the early stage and low-risk groups requires further studies.