Efficacy And Prognosis Analysis Of BTK Inhibitor-containing Combination Chemotherapy Regimen On PCNSL

Objective:The combination chemotherapy regimen containing Bruton tyrosine kinase(BTK)inhibitors may benefit patients with primary central nervous system lymphoma(PCNSL)by improving progression-free survival(PFS)and overall survival(OS).However,most research on BTK inhibitor combination chemotherapy regimens at home and abroad is still in the clinical trial phase,and there is limited existing data.Our aim is to evaluate the efficacy and adverse reactions of the combination chemotherapy regimen containing BTK inhibitors in real-world treatment scenarios for patients with PCNSL.Methods:We collected a total of 33 patients diagnosed with PCNSL in the Hematology Department of our hospital from January 2018 to January 2023,including 19 males and 14 females,with a median age of 62(range 33-76)years.Based on the induction treatment regimen,they were divided into two groups: observation group(15 cases)containing BTK inhibitors and control group(18 cases)without BTK inhibitors.The basic information of the collected patients includes blood routine,liver and kidney function,electrolytes,lactate dehydrogenase,coagulation indicators,biochemical and routine examination of cerebrospinal fluid,bone marrow cytology examination,peripheral blood smear,FISH detection,chromosomal karyotype analysis,head CT plain and enhanced scan,head MRI plain and enhanced scan,etc.Follow-up was conducted every 3 months by telephone or outpatient/inpatient system,recording drug-related adverse reactions,progression or death time during medication,and the last visit time.Results:1.The disease has a higher incidence in males than females,with a median age of 62 years and non-GCB subtype predominance.The median survival was 17 months(range: 2-62months),while the median PFS and OS were 18 months and 58 months,respectively.At2-year,3-year,and 5-year follow-up,the PFS rates were 27.1%,7.2%,and 0%,respectively,while the OS rates were 81.9%,76.1%,and 28.5%,respectively.2.The ORRs of the observation group and the control group were 93.3% and 77.8%,respectively(P=0.346),and there was no significant difference in ORR between the two groups(P>0.05).The median PFS of the observation group was 26 months,which was significantly longer than that of the control group(13 months,P=0.004),suggesting a potential benefit for PFS in the observation group.Although the difference in median OS between the observation and control groups was not statistically significant(the results did not reach 46 months,P=0.258),observing the survival curves showed a trend towards prolonged OS in the observation group compared to the control group.3.The observation group,which received BTK inhibitors,had a slightly higher incidence of hematologic adverse reactions ≥ grade 3 compared to the control group,with neutropenia occurring in 4 cases(26.7%),and thrombocytopenia and anemia each occurring in 3 cases(20.0%).However,the difference was not statistically significant(P>0.05).Non-hematologic adverse reactions in the observation group mainly included hypokalemia in10 cases(66.7%),respiratory infection in 5 cases(33.3%),hepatic insufficiency and hyperuricemia in 4 cases each(26.7%),gastrointestinal reactions in 3 cases(20.0%),and arrhythmia,rash,dyslipidemia,and renal insufficiency in 2 cases each(13.3%),with urinary tract infection occurring in 1 case(6.7%)and other reactions occurring in 2 cases(13.3%).The non-hematologic adverse reactions in the control group were similar to those in the observation group,with no significant differences in incidence of adverse events between the two groups(P>0.05).This suggests that the safety profile of the combination chemotherapy regimen containing BTK inhibitors is comparable to that of high-dose methotrexate alone,and does not increase the incidence of adverse events separately,showing good safety profile.4.MSKCC risk stratification and GCB subtype were found to be single-factor predictors of OS in PCNSL patients(P<0.10).However,this study did not find that MSKCC risk stratification and GCB subtype were independent factors affecting the prognosis of PCNSL.Age,ECOG score,number of deep lesions,blood LDH levels,cerebrospinal fluid protein levels,and IELSG score were not observed as prognostic factors for PCNSL patients in this trial,and their results had no statistical significance(P>0.05).Conclusion:1.The combination chemotherapy regimen containing BTK inhibitors exhibits superior ORR,prolongs PFS and OS of patients,and demonstrates higher efficacy compared to the methotrexate treatment group.2.The hematological adverse reactions are the main side effect of the combination chemotherapy regimen containing BTK inhibitors,and the difference between the two groups is not statistically significant compared to the methotrexate treatment group.This suggests that the safety of the combination chemotherapy regimen containing BTK inhibitors is equivalent to that of methotrexate alone,and does not increase the incidence of adverse events,indicating the safety of BTK inhibitors in the treatment of PCNSL.3.MSKCC risk stratification and GCB subtype are risk factors that affect the OS of PCNSL patients.Predicting the prognosis of patients can be achieved by using MSKCC risk stratification and GCB subtype,but it cannot explain whether age,ECOG score,number of deep lesions,blood LDH levels,CSF protein levels,and IELSG scores are prognostic factors for PCNSL patients.