目的:探讨基于维奈克拉(VEN)的诱导治疗在初治不宜强化化疗及复发难治(R/R)急性髓系白血病(AML)患者中的疗效及安全性。方法:回顾性分析西京医院血液内科于2021年2月1日至2022年4月30日收治的使用含维奈克拉诱导治疗的初治不适合强化化...目的:探讨基于维奈克拉(VEN)的诱导治疗在初治不宜强化化疗及复发难治(R/R)急性髓系白血病(AML)患者中的疗效及安全性。方法:回顾性分析西京医院血液内科于2021年2月1日至2022年4月30日收治的使用含维奈克拉诱导治疗的初治不适合强化化疗(初治虚弱组)及复发/难治性(R/R组)AML患者共51例的临床资料,分析患者的诱导治疗缓解率(CR/CRi)、总体反应率(ORR)、微小残留病(MRD)、治疗相关不良事件、总生存期(OS)及无进展生存期(PFS)。结果:初治虚弱组患者32例,中位年龄60(29-88)岁;R/R组患者19例,中位年龄49(22-92)岁。初治虚弱组和R/R组接受VEN治疗的中位疗程数均为2个。初治虚弱组及R/R组经1个疗程诱导治疗后CR/CRi率分别为65.6%和36.9%,ORR分别为81.3%和42.1%,经1-3个疗程治疗后累计CR/CRi率分别为71.9%和47.4%,达到CR/CRi患者的MRD转阴率分别为69.6%和33.3%。初治虚弱组及R/R组患者的中位PFS分别为8(5-11)和3(1-5)个月,中位OS分别为13(6-20)和5(3-7)个月。两组达到CR/CRi的患者中位OS均显著优于未达到CR/CRi的患者(13 vs 4个月、OS未达到vs 4个月)。首次诱导治疗期间有3级以上粒细胞、血红蛋白及血小板减少的患者分别占96%、90.2%、84.3%,粒细胞缺乏伴发热患者有30例(58.8%)。最常见的非血液学AE为感染(12/51,23.5%),其次为胃肠道反应(6/51,11.8%)。结论:以VEN为基础的治疗方案在初治不宜强化化疗及R/R AML患者中诱导治疗反应率高,总体耐受性良好,最常见的不良反应为血液学毒性及感染。展开更多
BACKGROUND Academic studies have proved that anti-programmed death-1(PD-1)monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma(cHL).However,most patients ultimately ...BACKGROUND Academic studies have proved that anti-programmed death-1(PD-1)monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma(cHL).However,most patients ultimately experienced failure or resistance.It is urgent and necessary to develop a novel strategy for relapsed/refractory cHL.The aim of this case report is to evaluate the combination approach of low-dose decitabine plus a PD-1 inhibitor in relapsed/refractory cHL patients with prior PD-1 inhibitor exposure.CASE SUMMARY The patient was a 27-year-old man who complained of enlarged right-sided cervical lymph nodes and progressive pain aggravation of the right shoulder over the past 3 mo before admission.Histological analysis of lymph node biopsy was suggestive of cHL.The patient experienced failure of eight lines of therapy,including multiple cycles of chemotherapy,PD-1 blockade,and anti-CD47 antibody therapy.Contrast-enhanced CT showed that the tumors of the chest and abdomen significantly shrunk or disappeared after three cycles of treatment with decitabine plus tislelizumab.The patient had been followed for 11.5 mo until March 2,2021,and no progressive enlargement of the tumor was observed.CONCLUSION The strategy of combining low-dose decitabine with tislelizumab could reverse the resistance to PD-1 inhibitors in patients with heavily pretreated relapsed/refractory cHL.The therapeutic effect of this strategy needs to be further assessed.展开更多
Despite the success of the combination of venetoclax with the hypomethylating agents(HMA)decitabine or azacitidine in inducing remission in older,previously untreated patients with acute myeloid leukemia(AML),resistan...Despite the success of the combination of venetoclax with the hypomethylating agents(HMA)decitabine or azacitidine in inducing remission in older,previously untreated patients with acute myeloid leukemia(AML),resistance-primary or secondary-still constitutes a significant roadblock in the quest to prolong the duration of response.Here we review the proposed and proven mechanisms of resistance to venetoclax monotherapy,HMA monotherapy,and the doublet of venetoclax and HMA for the treatment of AML.We approach the mechanisms of resistance to HMAs and venetoclax in the light of the agents’mechanisms of action.We briefly describe potential therapeutic strategies to circumvent resistance to this promising combination,including alternative scheduling or the addition of other agents to the HMA and venetoclax backbone.Understanding the mechanisms of action and evolving resistance in AML remains a priority in order to maximize the benefit from novel drugs and combinations,identify new therapeutic targets,define potential prognostic markers,and avoid treatment failure.展开更多
文摘目的:探讨基于维奈克拉(VEN)的诱导治疗在初治不宜强化化疗及复发难治(R/R)急性髓系白血病(AML)患者中的疗效及安全性。方法:回顾性分析西京医院血液内科于2021年2月1日至2022年4月30日收治的使用含维奈克拉诱导治疗的初治不适合强化化疗(初治虚弱组)及复发/难治性(R/R组)AML患者共51例的临床资料,分析患者的诱导治疗缓解率(CR/CRi)、总体反应率(ORR)、微小残留病(MRD)、治疗相关不良事件、总生存期(OS)及无进展生存期(PFS)。结果:初治虚弱组患者32例,中位年龄60(29-88)岁;R/R组患者19例,中位年龄49(22-92)岁。初治虚弱组和R/R组接受VEN治疗的中位疗程数均为2个。初治虚弱组及R/R组经1个疗程诱导治疗后CR/CRi率分别为65.6%和36.9%,ORR分别为81.3%和42.1%,经1-3个疗程治疗后累计CR/CRi率分别为71.9%和47.4%,达到CR/CRi患者的MRD转阴率分别为69.6%和33.3%。初治虚弱组及R/R组患者的中位PFS分别为8(5-11)和3(1-5)个月,中位OS分别为13(6-20)和5(3-7)个月。两组达到CR/CRi的患者中位OS均显著优于未达到CR/CRi的患者(13 vs 4个月、OS未达到vs 4个月)。首次诱导治疗期间有3级以上粒细胞、血红蛋白及血小板减少的患者分别占96%、90.2%、84.3%,粒细胞缺乏伴发热患者有30例(58.8%)。最常见的非血液学AE为感染(12/51,23.5%),其次为胃肠道反应(6/51,11.8%)。结论:以VEN为基础的治疗方案在初治不宜强化化疗及R/R AML患者中诱导治疗反应率高,总体耐受性良好,最常见的不良反应为血液学毒性及感染。
文摘BACKGROUND Academic studies have proved that anti-programmed death-1(PD-1)monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma(cHL).However,most patients ultimately experienced failure or resistance.It is urgent and necessary to develop a novel strategy for relapsed/refractory cHL.The aim of this case report is to evaluate the combination approach of low-dose decitabine plus a PD-1 inhibitor in relapsed/refractory cHL patients with prior PD-1 inhibitor exposure.CASE SUMMARY The patient was a 27-year-old man who complained of enlarged right-sided cervical lymph nodes and progressive pain aggravation of the right shoulder over the past 3 mo before admission.Histological analysis of lymph node biopsy was suggestive of cHL.The patient experienced failure of eight lines of therapy,including multiple cycles of chemotherapy,PD-1 blockade,and anti-CD47 antibody therapy.Contrast-enhanced CT showed that the tumors of the chest and abdomen significantly shrunk or disappeared after three cycles of treatment with decitabine plus tislelizumab.The patient had been followed for 11.5 mo until March 2,2021,and no progressive enlargement of the tumor was observed.CONCLUSION The strategy of combining low-dose decitabine with tislelizumab could reverse the resistance to PD-1 inhibitors in patients with heavily pretreated relapsed/refractory cHL.The therapeutic effect of this strategy needs to be further assessed.
文摘Despite the success of the combination of venetoclax with the hypomethylating agents(HMA)decitabine or azacitidine in inducing remission in older,previously untreated patients with acute myeloid leukemia(AML),resistance-primary or secondary-still constitutes a significant roadblock in the quest to prolong the duration of response.Here we review the proposed and proven mechanisms of resistance to venetoclax monotherapy,HMA monotherapy,and the doublet of venetoclax and HMA for the treatment of AML.We approach the mechanisms of resistance to HMAs and venetoclax in the light of the agents’mechanisms of action.We briefly describe potential therapeutic strategies to circumvent resistance to this promising combination,including alternative scheduling or the addition of other agents to the HMA and venetoclax backbone.Understanding the mechanisms of action and evolving resistance in AML remains a priority in order to maximize the benefit from novel drugs and combinations,identify new therapeutic targets,define potential prognostic markers,and avoid treatment failure.
