编者按：近年来，多发性骨髓瘤（MM）的治疗在CAR-T、多药联合、免疫治疗方面均取得了突破性的进展。随着新药不断被研发，患者的生存有了大幅度的提高。然而，在这个新药辈出的时代，造血干细胞移植（HSCT）在MM的治疗中是否可以被取代？美国威斯康星医学院Parameswaran Hari 教授在本届ASCO年会上的精彩报告似乎给出了答案。本刊在大会现场特邀请Hari 教授进行了专访。
Prof. Hari: The primary obstacle for allogeneic transplants in myeloma is the risk of treatment-related mortality. Allogeneic transplant is a risky treatment. Autotransplant and drugs are lower risk treatment than allotransplant. Allogeneic transplant in even the best centers carries the risk of treatment-related death somewhere between 5% and 8%. In the US， the overall 100-day mortality has come down to 8%. However， this is an unnecessary risk that patients have to face unless they have very high risk from the myeloma itself. That is the primary obstacle. Another is that the majority of patients with myeloma are above the age of seventy and that is an age at which we preferentially don’t do allotransplants because those patients usually don’t do so well. We should be limiting the procedure to younger patients and those at very high risk from the myeloma itself.
Prof. Hari: In our practice， we actually use allogeneic transplant for myeloma in patients that we call ultra-high risk. Ultra-risk means the risk of dying from myeloma is very high， as high as 50% in the first three years. Who are these patients? Firstly， they are patients with plasma cell leukemia with a lot of plasma cells in circulation (20% or more). The second group are those who are stage 3 plus have a high-risk cytogenetic marker. These patients usually have circulating plasma cells and high LDH， which are strong markers of high risk. Thirdly， patients who have relapsed within 18 months of their autotransplant. They get good induction treatment， then get an autotransplant and if they relapse within 18 months， their subsequent survival is very poor. Those are the patients who qualify for allotransplant.
Prof. Hari: I think autotransplant should be standard treatment for anybody who can get it in multiple myeloma. Within the last two years， we have had four studies. Dr Palumbo’s published in the New England Journal of Medicine and Dr Gay’s in Lancet Oncology， both of which showed that patients who went for an early transplant had a longer overall survival. The other two studies were presented by Dr Moreau at ASH， the IFM2009 study， and as presented here at ASCO， the EMN study by Dr Michele Cavo， have shown a longer progression-free survival but are not mature enough to show overall survival. So we have four studies all showing better progression-free survival if patients received a transplant upfront. Autotransplant upfront should be performed on anybody who can receive it based on their age， performance status and their health. To abandon autotransplant is saying that a patient does not need high-dose melphalan and we know that melphalan is a very effective drug against myeloma， so we should always be using autotransplant whenever we can use it. If someone doesn’t receive transplant upfront in the initial treatment， then they should get it later in treatment once they relapse if that occurs. For tandem autotransplants， in the United States， we don’t do too many. But in Europe， many countries still perform tandem autotransplants because the data are very impressive out of Europe. In the EMN study presented here at ASCO by Dr Cavo， several of the patients got tandem autotransplants and they did better， not statistically， but in the survival data， that group was the best followed by the single autotransplants followed by the delayed/no transplant group. In our practice in the US， we restrict tandem autotransplants to people who don’t get to complete remission after their first transplant and then we give them the choice of either a repeat autotransplant or a consolidation treatment like carfilzomib， lenalidomide and dexamethasone or bortezomib， lenalidomide and dexamethasone. As I have said， allotransplant should be restricted to those patients at very high risk， perhaps the top 10% of risky patients i.e. the young patients with plasma cell leukemia， ultra-high risk myeloma or those who have relapsed early after an autotransplant.
Prof. Hari: That is the question that has been addressed by Dr Cavo’s study. The EMN study had 1000 patients， one of the largest studies in myeloma， who were randomized to single or tandem autotransplants versus collection of stem cells but no transplant， but continuing on treatment and then everyone on to lenalidomide maintenance. In that study， the patients who had an early transplant benefited in terms of progression-free survival. The IFM2009 study from Dr Moreau had the same design (Velcade， lenalidomide， dexamethasone induction followed by consolidation for patients who did not receive a transplant versus transplant followed by Velcade， lenalidomide and dexamethasone) and the progression-free survival for early transplant was better. We don’t yet know overall survival in those two studies， but we do have studies that show overall survival benefits for early transplant. So skipping transplant， and more specifically， skipping early transplant， is associated with a lower survival， even with novel agents. That may change as the novel agents themselves improve. Having daratumumab and the monoclonal antibodies in the initial therapy may change those results， but historically， when we look at these studies from back in the 1990s， as the initial treatment got better， the benefit of transplant also got proportionately better and better. Transplant as we performed it in the 1990s can be skipped， but autotransplant as we practice now is associated with almost zero treatment-related mortality and excellent benefits， certainly in PFS， and in a couple of studies， overall survival. So it is not yet time to skip transplantation.