Decades ago, treatment for multiple myeloma (MM) was very limited and consisted mainly of alkylating agents and hormones; the goal of treatment was only to control disease progression, with an efficiency rate of about 50% and a very low complete remission (CR) rate, with an average survival of only 2-3 years. Because research into myeloma has been so slow, it has been considered an incurable disease for more than 30 years. Since the clinical application of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/ASCT), the discovery of interleukin-6 as a growth factor for MM cells by Japanese scholar Michio Kawano, and the subsequent development of new drugs targeting interleukin-6, the clinical treatment status of MM has been significantly improved. High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT / ASCT) has had a significant impact on the current state of myeloma treatment in three major ways: i) 15-30% of patients can achieve CR; ii) patients’ quality of life can be significantly improved; and iii) survival can be extended by more than 1 year. The biggest therapeutic change in the last decade has been the successful development of new drugs targeting interleukin-6, such as immunomodulators (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib). The survival of myeloma patients has been further prolonged compared to chemotherapy alone in the last century. Since the introduction of HDT/ASCT and new drugs, there has been a debate about the optimal treatment strategy for myeloma, such as is our ultimate treatment goal a “cure”? Or should we simply bring the disease under effective “control”? Let us first analyze the concept of “control” of the disease. The guiding principle of many patients and specialists in the treatment of MM is to simply “control” the disease, that is, to transform MM into a chronic disease, so that the patient survives for more than 20 years and has a good quality of life. Currently, this goal is difficult to achieve for MM. The reason is that even with HDT / ASCT and new drug therapy, the median survival is only 4-6 years for older patients and, for younger patients, usually around 8-10 years; in addition, almost all patients have to suffer the psychological burden of relapse many times until the disease progresses to a refractory state. Although the average life expectancy of MM patients was shortened by 18 years in the past era of chemotherapy, and can be extended by 8-10 years in the current era of new drug therapy, we are certainly not satisfied with the current average survival for a 53-year-old male patient. In summary, a cure is a worthwhile clinical treatment strategy to try and has the potential to make it a reality. The first report of a cure for MM was a patient who underwent allogeneic stem cell transplantation, but allogeneic stem cell transplantation has several problems: i) the high mortality rate associated with transplantation; ii) most patients of advanced age are not suitable for transplantation; and iii) the source of donors is very limited, making allogeneic stem cell transplantation suitable for only a few patients. With the widespread implementation of HDT/ASCT, 3-10% of patients with complete remission lasting more than 10 years can be considered as “transplant cured”, and if the percentage of such patients can be increased to 40-50%, we may consider MM as a potentially curable disease. In order to achieve the goal of “curing” MM, we believe that three measures are needed: i Eradication of tumor clones, including tumor stem cells. This is a prerequisite for curing the tumor and suggests that strong and effective therapeutic measures must be taken in the early stages of the disease to obtain optimal efficacy and maintenance. There is growing evidence that the more advanced the treatment of MM, the better the outcome, the longer the remission time, the less the number of recurrences, and the longer the survival of patients. Currently, the serologic indices we apply clinically are not sufficient to respond to the optimal efficacy of MM. Although eradication of tumor stem cells may be a necessary condition for the cure of most malignancies, there is growing evidence that residual tumor lesions can be effectively controlled with the continued action of the immune system, especially early in tumorigenesis, for example, early lesions in MM are monoclonal prolactinomycosis of undetermined significance (MGUS) and early lesions in low-grade malignant lymphoma are clonal benign lymphocytosis. Although sustained complete remission is a prerequisite for the cure of most MM, there are some patients who do not achieve complete remission and whose disease simply reverts to the MGUS state and can also achieve long-term survival. Presumably, these residual tumor stem cells are simply a clonal plasma cell that no longer has the ability to progress to malignant disease. Therefore, we need to be cautious in distinguishing this group of patients from those who are treated with insufficient intensity or with suboptimal results. In addition, there is a subset of MM patients who are susceptible to CR early in treatment and who also relapse early, as in Burkitt lymphoma. In such patients, it is appropriate to adopt short cycles of cis-chemotherapy to avoid rapid proliferation of tumor cells in order to achieve a cure. Therefore, we can obtain the prerequisites for a cure in patients with light yellow JIA JINCHEN〉male fighter aphidВ peal fan∮行У墓毯臀种瘟疲MM. ii Use the best examination indicators to judge the efficacy. Sensitive monitoring techniques can avoid treatment deficiencies and overtreatment, especially during the consolidation and maintenance phases of treatment. A sound judgment of efficacy also helps to reduce the cost of treatment and the toxic effects of drugs. Currently, the main methods to determine the efficacy of myeloma are the detection of M serum protein composition and bone marrow cytology. CR is a commonly used efficacy criterion, but it is not the best indicator and not a sensitive one. The best way to determine micro residual lesions in bone marrow is to use molecular biology techniques (e.g. quantitative PCR) and immunophenotyping (e.g. flow cytometry techniques); to determine extramedullary lesions is to use imaging techniques such as MRI and PET-CT. Genetic examination is also required for patients undergoing primary treatment to determine whether they are resistant to certain drugs, to avoid repeated dosing and drug toxicities, and also to select new treatment strategies based on genetic information. iii Manage the relationship between efficacy and drug toxicity to achieve the goals of improved quality of life, prolonged survival and ultimately a cure. In elderly patients (> 65-70 years) and in younger patients with severe complications, the goal of treatment is to prolong survival and improve quality of life. In elderly patients (> 85 years), the treatment goal should be to improve quality of life and to avoid expensive treatment options in cases of limited economic conditions. In younger patients (< 65 years), treatment regimens should be planned and designed with the goal of obtaining a cure. As in the treatment of Hodgkin's disease and acute lymphoblastic leukemia, we consider first the issue of cure and second the toxicity of the drugs. Younger patients with MM are our focus to move them from an incurable disease in the past to a potentially curable disease in the future. ASCT is generally used as the treatment of choice, but remains controversial on the grounds that other treatments can provide similar efficacy with lower toxicity. Our philosophy for a cure of MM should be to use the available drugs with proven efficacy to form the best treatment regimen, sequentially added to the application. And no longer apply alternative regimens with similar efficacy, but without improved survival. This treatment strategy was first reported by Cavo et al. The total treatment regimen, such as that of the Arkansas Study Group in the United States, combines multiple drugs during induction, consolidation and maintenance therapy for patients at low risk (GEP). After receiving this regimen, 89% of patients had CR for up to 4 years, which is equivalent to a cure in 50% of patients. Based on the above reports, we can say that MM has become a curable disease. It should be noted that, as in ALL, the most effective treatment strategy is not the size of the drug dose, but the frequency of drug use, i.e. the sequential application of an effective treatment regimen. It may be an incorrect philosophy to select treatment regimens based on the risk of the disease, using mild treatment regimens for low-risk patients and intense treatment regimens for high-risk patients. Therefore, in low- and intermediate-risk patients, ASCT was used to obtain an efficacy of VGPR or higher, followed by intensive treatment with VTD, and to date, patients who have achieved molecular remission have not seen relapse. Therefore, it may be a serious mistake to consider cure as the ultimate goal and to stop treatment after obtaining CR in low-risk patients. Currently, genetic indicators and other sensitive methods are being used to monitor the effect of treatment in order to select the appropriate treatment regimen. In summary, although we have gained an in-depth understanding of MM biology and have made great progress in the development of new drugs, we still cannot provide a cure for most patients in the near future. In order to achieve this goal of a cure, we must first recognize that MM is not a single individual. As with other malignant hematologic diseases, during the treatment of MM, we need to always adjust the treatment plan to suit each different subtype and achieve individualized treatment.