Retrospective Study Of The Efficacy And Safety Of Treatment With Subcutaneous Injection Of Bortezomib In De Novo Patients With MM

PartⅠ Retrospective study of the Efficacy and Safety of treatment withsubcutaneous injection of bortezomib in de novo patients with MM[Objective]To explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo multiple myeloma(MM)patients.[Methods]A total of 56 MM patients treated with bortezomib, adriamyc and dexamethasone form June 2008 to January 2015 were analyzed.Among them,29 received conventional PAD(PAD group)with the intravenous injection of bortezomib,another 28 received improved PAD(improved PAD group)with the subcutaneous injection of bortezomib. The efficacy and safety of two groups were analyzed.[Results](1)27 patients achieved stringent complete remission(s CR), complete remission(CR)or very good partial remission(VGPR) after 2 courses, PAD group and improved PAD group were 48.3% and 48.1%, respectively.After three courses or more of induction therapy, 29 patients achieved stringent complete remission(s CR), complete remission(CR)or very good partial remission(VGPR),PAD group and improved PAD group were 51.7% and 51.9% respectively,the difference was no statistically significant.(2)At the end of the follow-up,the median TTP time, PFS time and OS time of the PAD group was 47 months, 42 months, 63 months respectively, but the time of the improved PAD group wasn’t shown up yet.In the PAD group and improved PAD group,two years TTP rates,PFS rates and OS rates were 82.0% vs 94.4%,68.7% vs 94.4%,80.6% vs 100%.(3)After transplantation the effect of 13 patients was improved, the s CR+CR+VGPR rate and s CR +CR rate rose from 65.2% to 91.3% and from 26.1% to 60.9%,respectively. But the survival curve had no difference between the two arms.In the patients of transplantion the high-risk group by FISH and non-high risk group also had no difference.(4)The survival curve of the group of FISH high-risk was above the curve of the group without FISH high-risk,and followed up to 60 monthes,the OS rate of high-risk group was 61.9%,but the rate was only 39.2% in the group without FISH high-risk, although there was no statistically significant difference,but the clinical difference was obvious.Between the positive of 13 q deletion or t(4;14) or p53 deletion and the negative by FISH, the survival curves did not show significant difference.Between the patients with 1q21 amplificatin and negative by FISH, the OS curves showed significant statistical difference(P=0.039), and the negative group showed a trend of a longer time of PFS(P=0.068), but the TTP curve had no difference.(5)Risk stratification in FISH test results combined with ISS stage,divided into the high-rsk group of 23 cases(50%) and the risk group of 23 cases,the survival curves between the two groups did not show significant difference. But the rate of APBSCT was higher in the high-risk gruop(43.5% vs. 30.4%),and followed up to 60 monthes,the OS rate of the transplant group was 64.3%,but the rate was only 34.4% in the group without transplantion, although there was no statistically significant difference,but the clinical difference was obvious.(6)The study found that the hemoglobin,subcutaneous injection or 1q21+ were the prognosis factors for OS, while β2- MG has certain prognostic significance(P = 0.083), but the LDH and ISS staging in patients had not been found the prognostic significance.(7)The adverse events: Compared to PAD group,Grade 3 or worse adverse events were significantly reduced in improved PAD group, the most common were peripheral neuropathy(P=0.049), infection(0.004),the difference was statistically significant.When α =0.1, leukopenia(P=0.086), diarrhea(P=0.093) also showed statistically significant difference.[Conclusions]The improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had greatly improved the OS time, the hemoglobin,subcutaneous injection or 1q21+ were the prognosis factors for OS.Autologous hematopoietic stem cell transplantation could improve curative effect in de novo patients with MM,but it could not prolong the OS time,and in these people with or without FISH high-risk there was no need to transplant.The 13q14 deletion by FISH ware not associated with poorer outcomes in the treatment with bortezomib,the influence on prognosis was uncertain in t(4;14) and the p53 deletion,but 1q21 amplification was the poor prognostic factors,and the 1q21 amplification maybe responsible for the resistance of bortezomib.The FISH with t(4;14), the p53 deletion and 1q21 amplification should be determined early in de novo patients, at the same time to make sure the risk stratification, and it suggested that the APBSCT should be done in the patients with high-risk.PartⅡ Retrospective study of the efficacy of treatment with PDD vs.PAD in de novo patients with MM[Objective]To explore the effect of bortezomib, adriamyc or liposome doxorubicin and dexamethasone in de novo multiple myeloma(MM)patients,and the influence of the treatment depth on the survival curves.[Methods]A total of 96 MM patients treated with bortezomib, adriamyc or liposome doxorubicin and dexameth form June 2008 to January 2015 were analyzed.Among them, 38 received PDD with the liposome doxorubicin,another 59 received PAD with the adriamyc,in which the efficacy of different methods of use and the influence of the treatment depth on the survival curves were analyzed.[Results](1)Except 2 cases because of incomplete data failed to assess,among the remaining 94 cases,55 patients achieved VGPR or more, PDD group and PAD group were 69.2% and 50% respectively,the difference was statistically significant(P=0.042).21 patients achieved s CR or CR,PDD group and PAD group were 26.3% and 19.6% respectively.The 50-month follow up of these cases showed the overall survival rate in PDD group was 93.7% and 74.6% in PAD group.(2)Studies had shown that the better treatment effect, the later of disease recurrence, and the TTP curves had statistically significant differences(P=0.002), the PFS and OS curves had no statistical difference.(3)Between the s CR/CR group and the VGPR or less group, the TTP curves showed significant difference(P = 0.039), the PFS and OS curves had no statistically difference, but followed up to 70 monthes,the OS rate of the s CR/CR group was 76.4%,but the rate was only 25.5% in the other group.(4)Compared the s CR+CR+VGPR group and the PR or less group, the TTP and the PFS curves showed significant difference, At the same time followed up to 58 monthes,the OS rate of the s CR+CR+VGPR group was 63.3% and the rate was 52.2% in the other group,but there was no significant differences between two groups.(5)The TTP between the s CR/CR group and the VGPR group showed significant difference(P = 0.044), the PFS curves were intertwined and showed no difference. Even though its OS curve also had not yet showed statistically significant, but the follow-up of 70 months, in s CR/CR group 54.5% of the patients survived, but the survival rate was only 38.5% in the VGPR group, clinical difference was obvious.[Conclusions]PDD solution by changing from adriamyc to liposome doxorubicin significantly improve the effect of the de novo MM patients, and people in PDD group had a better OS.The treatment depth affected the TTP, PFS time and OS time greatly, the patient who obtained CR had longer OS time, in the treatment of the de novo multiple myeloma patients we should seek to higher curative effect.