不同化疗方案治疗初治多发性骨髓病患者的近期疗效、生存时间及毒副作用
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摘要
目的:探讨TCD方案和BCD方案对新诊多发性骨髓病(初治MM)患者近期疗效、生存时间及毒副作用。方法:收集我院2011年1月-2018年1月收治的初治患者106例临床资料。106例患者分为2组:1组53例用沙利度胺(Thalidomide)、环磷酰胺(Cyclophosphamide)和地塞米松(Dexamethasone)组成的化疗方案治疗(TCD组),另1组53例用硼替佐米(Bortezomib)、环磷酰胺和地塞米松组成的化疗方案治疗(BCD组)。比较2组的疗效、中位PFS、中位OS时间及毒副作用发生率,同时分析缓解程度、亚组因素与疗效间的相关性。结果:2组患者≥MR率比较差异无显著性(P>0.05);BCD组患者≥PR率、≥VGPR率及CR率均显著高于TCD组(P<0.05);BCD组患者中位PFS显著长于TCD组(P<0.05);2组患者中位OS比较差异无显著性(P>0.05)。TCD组疗效≥MR患者的中位OS时间显著长于0.05)。BCD组患者中ISS分期III期、R-ISS分期II期及肾功能正常者的ORR显著高于TCD组(P<0.05)。2组感染、乏力、消化道反应及骨髓抑制发生率比较差异无显著性(P>0.05);BCD组末梢神经麻木和带状疱疹发生率均显著高于TCD组(P<0.05)。结论:TCD方案和BCD方案治疗初治MM的总体疗效接近,其中BCD方案的应用有助于提高缓解程度,延长PFS时间;而TCD方案应用在降低毒副作用发生风险,提高患者治疗耐受性方面具有优势。
Objective: To investigate the short-term therapeutic efficacy, survival time and side effects in newly diagnosed multiple myeloma patients treated with TCD regimen consisted of thalidomide, cyclophosphiamide and dexamethasone, and BCD reginen consisted of bortezomib, cyclophsphamide and dexamethasone. Methods: The clinical data of newly diagnosed MM patients admitted in our hospital from January 2011 to January 2018 were collected and analyzed retrospectively. According to chemotherapectic regimen, 106 patients were divided into 2 groups: 53 cases in one group were treated with TCD regimen(TCD group), and 53 cases in another group were treaded with BCD regimen(BCD group). The therapeutic efficacy, median PFS and OS time and incidence of side effects in 2 groups were compared, at the same time the relationship of the remission degree and the factors in different subgroups with the therapeutic efficacy was analyzed in 2 groups. Results: There was no significant difference in the ≥ MR rate between2 groups(P>0.05). The ≥ PR rate, ≥ VGPR rate and CR rate of BCD group were significantly higher than TCD group(P<0.05). The median PFS time of patients in BCD group were significantly longer than that in TCD group(P<0.05). There was no significant difference in the median OS time of patients between 2 groups(P<0.05). The median OS time of ≥ MR patients in TCD group was significantly longer than that of < MR patients(P<0.05). The median OS time of ≥ PR patients in TCD group were significantly longer than that of < PR patients(P<0.05). The median OS time of ≥ VGPR patients in BCD group was significantly longer than that of < VGPR patients(P<0.05). There was no significant difference in the median OS time of ≥ PR and < PR patients in BCD group(P>0.05). The ORR of≥ VGPR patients in BCD group was significantly higher than that in TCD group(P<0.05). There was no significant difference in the incidence of infection, fatigue, gastrointestinal reactions and bone marrow suppression between 2 groups(P<0.05). The incidence of numbness in distal extremities and herpes zoster in BCD group was significantly higher than that in TCD group(P<0.05). Conclusion: TCD and BCD in the treatment of patients with NDMM possess the same disease control effects; BCD regimen application can efficiently improve remission degree and prolong PFS time; but TCD regimen application have the advantages in reducing the side effects risk and improving treatment tolerance.
Objective: To investigate the short-term therapeutic efficacy, survival time and side effects in newly diagnosed multiple myeloma patients treated with TCD regimen consisted of thalidomide, cyclophosphiamide and dexamethasone, and BCD reginen consisted of bortezomib, cyclophsphamide and dexamethasone. Methods: The clinical data of newly diagnosed MM patients admitted in our hospital from January 2011 to January 2018 were collected and analyzed retrospectively. According to chemotherapectic regimen, 106 patients were divided into 2 groups: 53 cases in one group were treated with TCD regimen(TCD group), and 53 cases in another group were treaded with BCD regimen(BCD group). The therapeutic efficacy, median PFS and OS time and incidence of side effects in 2 groups were compared, at the same time the relationship of the remission degree and the factors in different subgroups with the therapeutic efficacy was analyzed in 2 groups. Results: There was no significant difference in the ≥ MR rate between2 groups(P>0.05). The ≥ PR rate, ≥ VGPR rate and CR rate of BCD group were significantly higher than TCD group(P<0.05). The median PFS time of patients in BCD group were significantly longer than that in TCD group(P<0.05). There was no significant difference in the median OS time of patients between 2 groups(P<0.05). The median OS time of ≥ MR patients in TCD group was significantly longer than that of < MR patients(P<0.05). The median OS time of ≥ PR patients in TCD group were significantly longer than that of < PR patients(P<0.05). The median OS time of ≥ VGPR patients in BCD group was significantly longer than that of < VGPR patients(P<0.05). There was no significant difference in the median OS time of ≥ PR and < PR patients in BCD group(P>0.05). The ORR of≥ VGPR patients in BCD group was significantly higher than that in TCD group(P<0.05). There was no significant difference in the incidence of infection, fatigue, gastrointestinal reactions and bone marrow suppression between 2 groups(P<0.05). The incidence of numbness in distal extremities and herpes zoster in BCD group was significantly higher than that in TCD group(P<0.05). Conclusion: TCD and BCD in the treatment of patients with NDMM possess the same disease control effects; BCD regimen application can efficiently improve remission degree and prolong PFS time; but TCD regimen application have the advantages in reducing the side effects risk and improving treatment tolerance.
引文
1 Caers J,Fernández de Larrea C,Leleu X,et al.The changing landscape of smoldering multiple myeloma:a European perspective.Oncologist,2016;21(3):333-342.
2 Einsele H,Engelhardt M,Tapprich C,et al.Phase II study of bortezomib,cyclophosphamide and dexamethasone as induction therapy in multiple myeloma:DSMM XI trial.Br J Haematol,2017;179(4):586-597.
3 Kumar SK,Dispenzieri A,Lacy MQ,et al.Continued improvement in survival in multiple myeloma:changes in early mortality and outcomes in older patients.Leukemia,2014;28(5):1122-1128.
4中国医师协会血液科医师分会.中国多发性骨髓瘤诊治指南(2017年修订).中华内科杂志,2017;56(11):866-870.
5王建祥.血液病诊疗规范.北京.中国协和医科大学出版社,2014:127-128.
6 Richardson PG,Hungria VTM,Yoon SS,et al.Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma:outcomes by prior treatment.Blood,2016;127(6):713-721.
7 Shah SP,Nooka AK,Jaye DL,et al.Bortezomib-induced heat shock response protects multiple myeloma cells and is activated by heat shock factor 1 serine 326 phosphorylation.Oncotarget,2016;7(37):59727-59741.
8 Ong SY,Ng HY,Surendran S,et al.Subcutaneous bortezomib combined with weekly cyclophosphamide and dexamethasone is an efficient and well tolerated regime in newly diagnosed multiple myeloma.Br J Haematol,2015;169(5):754-756.
9 Palumbo A,Avet-Loiseau H,Oliva S,et al.Revised intemational staging system for multiple myeloma:a report from International Myeloma Working Group.J Clin Oncol,2015;33(26):2863-2869.
10 Shah JJ,Feng L,Thomas SK,et al.Siltuximab(CNTO 328)with lenalidomide,bortezomib and dexamethasone in newly-diagnosed,previously untreated multiple myeloma:an open-label phase I trial.Blood Cancer J,2016;6(2):e396.
11 Ozaki S,Tanaka O,Fujii S,et al.Therapy with bortezomib plus dexamethasone induces osteoblast activation in responsive patients with multiple myeloma.Int J Hematol,2018;86(2):180-185.
12 Hungria VT,Crusoe EQ,Maiolino A,et al.Phase 3 trial of three thalidomide·-containing regimens in patients with newly diagnosed multiple myeloma not transplant-eligible.Ann Hematol,2016;95(2):271-278.
13 Weisel K,Doyen C,Dimopoulos M,et al.A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation.Leuk Lymphoma,2017;58(1):153-161.
14 Palumbo A,Rajkumar SV,San Miguel JF,et al.International Myeloma Working Group consensus statement for the management,treatment,and supponive care of patients with myeloma not eligible for standard autologous stem-cell transplantation.J Clin Oncol,2014;32(6):587-600.
15 Cavo M,Pantani L,Pezzi A,et al.Bortezomib-thalidomidedexamethasone(VTD)is superior to bortezomib-cyclophospha midedexamethasone(VCD)as induction therapy prior to autologous stem cell transplantation in multiple myeloma.Leukemia,2015;29(12):2429-2431.
2 Einsele H,Engelhardt M,Tapprich C,et al.Phase II study of bortezomib,cyclophosphamide and dexamethasone as induction therapy in multiple myeloma:DSMM XI trial.Br J Haematol,2017;179(4):586-597.
3 Kumar SK,Dispenzieri A,Lacy MQ,et al.Continued improvement in survival in multiple myeloma:changes in early mortality and outcomes in older patients.Leukemia,2014;28(5):1122-1128.
4中国医师协会血液科医师分会.中国多发性骨髓瘤诊治指南(2017年修订).中华内科杂志,2017;56(11):866-870.
5王建祥.血液病诊疗规范.北京.中国协和医科大学出版社,2014:127-128.
6 Richardson PG,Hungria VTM,Yoon SS,et al.Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma:outcomes by prior treatment.Blood,2016;127(6):713-721.
7 Shah SP,Nooka AK,Jaye DL,et al.Bortezomib-induced heat shock response protects multiple myeloma cells and is activated by heat shock factor 1 serine 326 phosphorylation.Oncotarget,2016;7(37):59727-59741.
8 Ong SY,Ng HY,Surendran S,et al.Subcutaneous bortezomib combined with weekly cyclophosphamide and dexamethasone is an efficient and well tolerated regime in newly diagnosed multiple myeloma.Br J Haematol,2015;169(5):754-756.
9 Palumbo A,Avet-Loiseau H,Oliva S,et al.Revised intemational staging system for multiple myeloma:a report from International Myeloma Working Group.J Clin Oncol,2015;33(26):2863-2869.
10 Shah JJ,Feng L,Thomas SK,et al.Siltuximab(CNTO 328)with lenalidomide,bortezomib and dexamethasone in newly-diagnosed,previously untreated multiple myeloma:an open-label phase I trial.Blood Cancer J,2016;6(2):e396.
11 Ozaki S,Tanaka O,Fujii S,et al.Therapy with bortezomib plus dexamethasone induces osteoblast activation in responsive patients with multiple myeloma.Int J Hematol,2018;86(2):180-185.
12 Hungria VT,Crusoe EQ,Maiolino A,et al.Phase 3 trial of three thalidomide·-containing regimens in patients with newly diagnosed multiple myeloma not transplant-eligible.Ann Hematol,2016;95(2):271-278.
13 Weisel K,Doyen C,Dimopoulos M,et al.A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation.Leuk Lymphoma,2017;58(1):153-161.
14 Palumbo A,Rajkumar SV,San Miguel JF,et al.International Myeloma Working Group consensus statement for the management,treatment,and supponive care of patients with myeloma not eligible for standard autologous stem-cell transplantation.J Clin Oncol,2014;32(6):587-600.
15 Cavo M,Pantani L,Pezzi A,et al.Bortezomib-thalidomidedexamethasone(VTD)is superior to bortezomib-cyclophospha midedexamethasone(VCD)as induction therapy prior to autologous stem cell transplantation in multiple myeloma.Leukemia,2015;29(12):2429-2431.