Effect Of Cumulative Bortezomib Dose On Survival In Multiple Myeloma Patients Receiving Bortezomib-containing Regimens

Multiple myeloma(MM)is a malignant neoplasm of plasma cells that accumulate in bone marrow,leading to bone destruction and marrow failure.The number of patients with multiple myeloma(MM)is rapidly increasing in recent years and is closely related to the age.With the increase of age,the incidence of MM is also increasing.MM is typically sensitive to a variety of cytotoxic drugs,both as initial treatment and as treatment for relapsed disease.Unfortunately responses are typically durable,and MM is not considered curable with current approaches.Bortezomib,a first-in-class proteasome inhibitor,has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma.Clinical evidence has shown that bortezomib is active in myeloma.There are many studies on a single bortezomib dose(either standard dose or dose reduction,high dose)in the treatment of multiple myeloma,but few studies on the relationship between the survival in multiple myeloma patiens and the cumulative bortezomib dose.The retrospective analysis is to investigate whether increased cumulative bortezomib dose could improve the prognosis of MM patiens.Part oneObjective:To explore the effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib-containing regimens.Methods:A retrospective analysis were performed on the clinical characteristics,laboratory examination and therapeutic options of 172 cases of MM patients.The cumulative bortezomib dose 21mg/m~2 was selected as the cut-off for defining the dose group to be compared for OS.172 cases of MM patients were divided into A(<21mg/m~2)and B(≥21mg/m~2)two groups.Until observation time,54 cases of MM patients receiving TTP were divided into C(<21mg/m~2)and D(≥21mg/m~2)two groups.91 cases of MM patients receiving PFS were divided into E(<21mg/m~2)and F(≥21mg/m~2)two groups.35 cases of MM patients receiving DFS were divided into G(<21mg/m~2)and H(≥21mg/m~2)two groups.Patient characteristics were well balanced between two groups(A and B).Differences in baseline characteristics between groups were analyzed using the Student’s t-test for continuous variables and the chi-square test for categorical variables.Distributions were estimated using the Kaplan–Meier method.Differences in OS between groups were then analyzed using the log-rank tests.To account for potential differences in baseline characteristics between groups,a preplanned sensitivity analysis was conducted,whereby the Cox proportional hazards model was adjusted for discordant characteristics.Results:OS was significantly longer in the higher(≥21mg/m~2)versus lower(<21mg/m~2)cumulative bortezomib dose group(median 73.53 VS 18.9 months,P<0.001 Log-rank);TTP was significantly longer in the higher(≥21mg/m~2)versus lower(<21mg/m~2)cumulative bortezomib dose group(median 22.03 VS 4.67 months,P<0.01 Log-rank).PFS was significantly longer in the higher(≥21mg/m~2)versus lower(<21mg/m~2)cumulative bortezomib dose group(median 22.03 VS 5.53 months,P<0.01 Log-rank).There was no difference in DFS between two groups.The study did not reveale an increased incidence of serious AEs in the higher versus lower cumulative bortezomib dose group.Conclusion:A higher cumulative dose of bortezomib may result in improved OS,TTP,PFS in MM patients,but not DFS.The study did not reveale an increased incidence of serious AEs in the higher versus lower cumulative bortezomib dose group.Part TwoObjective:To explore the effect of cumulative bortezomib dose on survival in multiple myeloma patients with poor prognosis.Methods:Of 172 cases of MM patients,54 cases of MM patients with age≥65y,100 cases of MM patients with HB<100g/l,66 cases of MM patients with ALB<35g/l,89 cases of MM patients with β2-MG≥5.5 mg/l,40 cases of MM patients with Scr≥177umol/l,91 cases of MM patients with clonal bone marrow plasma cells≥30%,127 cases of DS ⅢMM patients,25 cases of MM patients with CD56 negative,55 cases of MM patients with poor cytogenetic abnormalities.The cumulative bortezomib dose 21mg/m~2 was selected as the cut-off for defining the dose group to be compared for OS.These cases of MM patients were divided into one(<21mg/m~2)and two(≥21mg/m~2)two groups.Distributions were estimated using the Kaplan–Meier method.Differences in OS between groups were then analyzed using the log-rank tests.Results:OS was significantly longer in the higher(≥21mg/m~2)versus lower(<21mg/m~2)cumulative bortezomib dose group(P<0.05 Log-rank)in any analysis on these poor prognosis.Correlation analysis indicates that two variables(cumulative bortezomib dose with OS/TTP/PFS)are perfectly related in a positive linear sense.There is no linear relationship between the two variables(the time to 21mg/m~2 with OS).Conclusion:A higher cumulative dose of bortezomib may result in improved OS in MM patients with poor prognosis.Two variables(cumulative bortezomib dose with OS/TTP/PFS)are perfectly related in a positive linear sense.