尽管近二十年来，随着新药物和新疗法的问世，多发性骨髓瘤（MM）患者的生存得到显著改善。但对于不适合进行骨髓移植的群体，他们的生存期限相对较短，因此，迫切需要探索新的治疗方案来改善他们的预后情况。在近期召开的第29届欧洲血液协会年会（EHA 2024）上，国际骨髓瘤工作组(IMWG)委员、法国里尔大学医院Thierry Facon教授口头报告了关键研究IMROZ结果，该研究探讨了伊沙妥昔单抗联合VRD方案（Isa-VRD）治疗新诊断不适合移植MM患者的效果，并已于今年6月初发表于NEJM。《肿瘤瞭望-血液时讯》现场特邀Thierry Facon教授分享IMROZ研究的重要发现及其意义。

 

Thierry Facon教授：IMROZ研究是一项大型、Ⅲ期、随机、国际性研究，针对新诊断不适合移植的多发性骨髓瘤患者。该研究的目的是评估将抗CD38单克隆抗体伊沙妥昔单抗加入VRD方案（硼替佐米、来那度胺和地塞米松）的临床价值。我们招募了446名年龄在80岁以下的患者，随机分配接受伊沙妥昔单抗+VRD（Isa-VRD）或VRD方案治疗，以无进展生存期（PFS）为主要终点。

 

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Oncology Frontier-Hematology Frontier：At this EHA conference，you reported the breakthrough results of IMROZ research.Firstly，could you please introduce the background and main design of this study?

 

Professor Thierry Facon：The IMROZ study is a very large，phase three，randomized international study designed for newly diagnosed transplant-ineligible patients with multiple myeloma.The purpose of the study was to assess the clinical value of adding isatuximab，an anti-CD38 monoclonal antibody，to the VRD regimen(bortezomib，lenalidomide，and dexamethasone).We enrolled 446 patients below the age of 80 years，who were randomly allocated to either VRd or isatuximab VRd，with progression-free survival(PFS)as the primary endpoint.

 

Thierry Facon教授：主要终点PFS在大约五年的中位随访期内达成。Isa-VRD组的中位PFS尚未达到，而VRD组为54个月。五年PFS率VRD组为45%，Isa-VRD组为63%。Isa-VRD组相较VRD组的风险比为0.59，意味着进展或死亡风险降低40%。两组间具有临床上和统计学上的显著差异。

 

除了PFS，我们还观察到一些关键次要终点，尤其是完全缓解或更好以及MRD阴性率。在Isa-VRD组75%的患者达到了完全缓解或更好的效果，而VRd组为64%。Isa-VRD组中55.5%的患者达到了MRD阴性，而VRd组为41%。最重要的是，我们观察了持续的MRD阴性，在Isa-VRD组中这一比例几乎翻倍（Isa-VRD组47%vs.VRd组24%)。因此，Isa-VRD方案与深度缓解有关，包括MRD阴性和持续MRD阴性。

 

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Oncology Frontier-Hematology Frontier：In the IMROZ study，the Isa VRD regimen significantly extended the progression free survival(PFS)of patients compared to the VRD regimen.Can you explain in detail the advantages of this treatment combination?What is its therapeutic mechanism?

 

Professor Thierry Facon：The primary endpoint of PFS was met with a median follow-up of approximately five years.The median PFS was not reached for the isatuximab VRD arm and was 54 months for the VRD arm.The five-year PFS rates were 45%for VRD and 63%for isatuximab VRD.The hazard ratio was 0.59，representing a 40%reduction in the risk of progression or death.That’s a very clinically significant and very statistically significant difference between the two arms.

 

Besides the PFS，we had some key secondary endpoints，especially complete response or better，and MRD negativity.So in the isatuximab VRd arm，almost 75%of patients achieved a complete response or better compared to 64%of patients in the VRd arm.MRD-negative complete response was seen in 55.5%of patients in the isatuximab VRd arm versus 41%of patients in the VRd arm.And most importantly，we looked at sustained MRD negativity，and sustained MRD negativity was almost double in the isatuximab VRd arm，from 24%in the VRd arm to 47%in the isatuximab VRd arm.So this isatuximab VRd regimen was associated with deep response rates，including MRD negativity and sustained MRD negativity.

 

Thierry Facon教授：Isa-VRD的安全性良好且耐受性好。两组之间的生活质量没有差异。我还应该提到生存期，总体生存期（OS）尚未成熟，但有利于Isa-VRD的趋势，VRd组的五年生存率为65%，而Isa-VRD为72%，意味着死亡风险减少22%。尽管Isa-VRD组的3级及以上不良事件略多，但这可能是由于治疗时间更长。VRD组的中位治疗时间为31个月，而Isa-VRD组为53个月。按暴露调整的发生率，两组之间相似。

 

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Oncology Frontier-Hematology Frontier：The IMROZ study not only focuses on the progression free survival of patients，but also on the safety of treatment and the quality of life of patients.Could you please introduce how the Isa-VRD protocol performs in terms of safety in the IMROZ study?What is the incidence of adverse reactions compared to VRD?Has the patient’s quality of life improved?

 

Professor Thierry Facon：The safety profile of isatuximab VRD was favorable and well-tolerated.There was no difference in terms of quality of life between the two arms.I should also have said that for survival，overall survival is still immature，but with a trend in favor of isatuximab VRd，the five-year survival is 65%for VRd versus 72%for isatuximab VRd，representing a 22%reduction in the risk of death.Although there were slightly more grade 3 or higher adverse events and grade 5 adverse events in the isatuximab VRD arm，this was likely due to the longer treatment duration.The median treatment duration was 31 months for VRD versus 53 months for isatuximab VRD.When looking at exposure-adjusted incidence rates，they were somewhat similar between the two arms.

 

Thierry Facon教授：IMROZ研究将确立Isa-VRD作为新诊断且不适合移植老年多发性骨髓瘤患者的新治疗标准。这是一项重大成就，在这个人群中的中位PFS可能超过80个月。未来的发展可能包括使用双特异性抗体和CAR-T细胞疗法，尤其是对于老年患者，我们也在不断改进治疗方案和结果。

 

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Oncology Frontier-Hematology Frontier：What new development directions do you think will be in the field of multiple myeloma treatment in the future?Can we expect more effective treatment options to emerge for NDMM patients who are not suitable for transplantation?

 

Professor Thierry Facon：The IMROZ study will establish isatuximab VRD as a new standard of care for elderly patients with newly diagnosed multiple myeloma not eligible for transplant.This is a significant achievement，with the median PFS likely exceeding 80 months in this population.Future developments may include the use of bispecific antibodies and CAR T-cell therapies，even for elderly patients，as we continue to improve treatment options and outcomes.

Thierry Facon教授：好的。我对中国非常了解。我在中国参加了许多会议。我本月底将会在上海。并且我可能会在年底前再次来到中国。在过去的15年里，我访问了大约30个中国城市。您的观点很好，因为IMROZ研究中有中国的患者和研究中心。正如您所知，这项研究已于6月初发表在《新英格兰医学杂志》(NEJM)上，其中一位合作者来自沈阳，是您的同胞。

 

我今天上午在新闻发布会上展示的研究以及明天将在全体会议上展示的研究，均涉及中国患者。在本次意向性分析（ITT）人群中，有12名中国患者。同时，另外有38名患者在另一项中国扩展研究中接受治疗。这意味着基本上有50名中国患者在类似研究中接受了VRd或Isa-VRD治疗。因此，这可能会得到中国药监局的批准，这项研究对中国在许多方面都很重要，在此也向中国研究人员表示祝贺和感谢。

 

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Oncology Frontier-Hematology Frontier：I would like to ask you the final question.What do you think about Chinese doctors and clinics?What do you want to say to them?

 

Professor Thierry Facon：Okay.I know your country quite well.I did many meetings in China.I will be in Shanghai at the end of this month，and I will likely be back to China before the end of the year.I have visited，let’s say，something like 30 different cities in China in the past 15 years.The good point is that your point is well taken because IMROZ has Chinese patients，Chinese centers.As you know，the study has been published early June in the New England Journal of Medicine，and one co-author is from Shenyang，from your country.

 

The study I have presented this morning at the press meeting and I will present at the plenary session tomorrow，includes Chinese patients.So we have 12 patients in this ITT population，but China also had an extension study.12 patients are in IMRO，and an additional 38 patients have been treated in a different Chinese study.This means that basically there is a group of 50 Chinese patients having received either VRd or isatuximab VRd in the context of this similar study.So that will likely lead to approval by the Chinese FDA，so the study is important for China in many ways，but it’s also a good opportunity to congratulate and thank Chinese investigators.

 

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