Criteria for remission Monitoring of MM remission assessment began in the 1960s and was primarily based on a reduction of 15 g/l or more of M protein in the blood or an increase of 2 g/dl or more of hemoglobin. The definition of remission was subsequently proposed as at least a 50% reduction in monoclonal material, and given that extramedullary lesions are also an important part of the response, a reduction of at least 50% in plasmacytoma was required. The Southwest Oncology Chemotherapy Study Group (SWOG) also established corresponding criteria, taking into account the decrease in the synthetic index of serum M-protein and urinary light chain proteins, as well as the correction of hypoproteinemia and anemia. It was not until the late 1990s that a new, almost worldwide, criterion was adopted. In brief, CR requires the disappearance of primitive myeloma proteins in serum and urine immunofixation electrophoresis and proof of less than 5% bone marrow plasma cells. Partial remission (PR) requires a 50% or greater reduction in serum M protein and a 90% or greater reduction in urinary M protein and/or <200 mg/24h, and a 50% or greater reduction in the cross-sectional area of the extramedullary plasmacytoma area. Minimal remission (MR) requires a 25% or greater reduction in serum M protein, a 50% or greater reduction in urinary M protein, and a 25% or greater reduction in the cross-sectional area of the extramedullary plasmacytoma area. Importantly, remission of any kind should be maintained for a minimum of 6 weeks. Ten years later, a new international system of remission was proposed based on the previous classification system and characterized in Table 1. this classification is the standard for remission currently in use worldwide. Complete remission Obtaining CR with negative serum and urine immunofixation electrophoresis is very important and this has been demonstrated in a variety of studies. In the context of autologous hematopoietic stem cell transplantation (ASCT), it has been demonstrated that the patients who can really benefit are those who obtain CR after transplantation. Other studies have also demonstrated a better prognosis for long-term survival after ASCT, with approximately 20-30% of patients achieving sustained CR without relapse for more than 10 years, indicating a so-called "cure grade" or "opto-cure". Interestingly, those who obtained VGPR did not have a better prognosis than those who obtained PR. There is no doubt that obtaining an immunofixation electrophoresis-negative CR in transplantation is a critical step before obtaining long-term remission and survival in MM. Recent reports have also clearly demonstrated that achieving an IFE-negative CR in elderly patients treated with a combination of marfalan and prednisone plus novel antimyeloma drugs with also have a significant impact on their survival. Furthermore, the ultimate goal is sustained remission over time, as there is evidence that sustained CR has an important role in prolonging survival, especially in high-risk patients. Indeed, the prognosis of patients who undergo high-dose chemotherapy/ ASCT (non-sustained CR) and lose their CR status within 1 year is extremely poor; this subgroup can be identified by cytogenetics and multiparametric flow cytometry persistent microscopic residual lesions (MRD) detected by FISH at high risk at baseline after ASCT. Another important aspect to take into account is the presence of oligoclonal bands that should be taken into account when commenting on serum CR. The appearance of an oligomono-clonal humoral response, which arises after the disappearance of serum M protein, is a different event from that observed at the time of diagnosis in MM after ASCT, which has been recognized as a benign phenomenon. The mechanism of this restricted antibody response cannot be accounted for by a specific immune humoral or cellular component, but may be due to two losses of normal control of T-cell proliferation of B-cells, altered affinity of mature B-lymphocytes or failure of memory response to several antigens. Although initially described as transient, there is growing evidence that this oligomeric immune response can persist for several years. Furthermore, the initial treatment to obtain CR includes newer drugs such as lenalidomide, thalidomide and bortezomib, which results in oligoclonal bands in up to 60%, which is a higher emergence than the use of conventional induction standard cytotoxic therapies prior to ASCT. Whether this phenomenon is due to greater tumor shrinkage or more robust immune reconstitution is unknown. In comparison with other degrees of remission, this oligomeric phenomenon is almost exclusively restricted to patients with CR and is associated with a significantly longer progression-free survival and overall survival. At the time of relapse, a reappearance of the stripes from the initial diagnosis can be seen. Furthermore, with the availability of new technologies in biomedicine, achieving an IFE-negative CR should no longer be the ultimate goal of MM treatment. In this regard, the assessment of sCR should be investigated and bone marrow remission should be explored beyond morphological aspects. However, this assessment is mandatory in serologic CR. Despite EBMT and IMWG recommendations, bone marrow examination can be removed in patients with negative immunofixation electrophoresis in clinical practice. However, bone marrow morphology is a simple, inexpensive and non-time-consuming test to throw and it should be the preferred step to evaluate tumor lesions in patients with myeloma and in patients with negative IFE after transplantation. In the Mayo Clinic's experience, patients with less than 5% plasma cells in their bone marrow during the process of achieving IFE-negative status had improved overall survival compared to those with 5% or more plasma cells in their bone marrow. In recent studies, the percentage of plasma cells in the bone marrow in MM patients with post-transplant CR has a great predictive value for prognosis, as recently reported by multiparametric flow cytometry (MFC) or molecular studies. The main method for further identification of microresidual lesions (MRD) in the bone marrow is flow cytometry (FCM) testing, as is the standard for other malignant hematologic diseases such as acute leukemia. This technique is rapid, available for almost all patients, and is available and affordable at most institutions. The presence of malignant plasma cells after detection in the bone marrow by ASCT by FCM has been identified as an important prognostic factor in MM. In this sense, MRD detected by FCM at 100 days post-transplantation even with CR in serum was correlated with progression-free survival and overall survival in multivariate analysis. Deeper remission can also be assessed by molecular biology studies. For example, qPCR (quantitative real-time PCR) is used in malignant plasma cells to target heavy chain gene rearrangements. Using this technique, sustained molecular CR has been associated with ASCT and a good prognosis after allografting. The disadvantages of molecular studies are that they are time-consuming, resource-intensive and available only in a subset of patients. Both techniques (molecular and MFC) have the general limitation of the possibility of patchy infiltration of malignant plasma cells in the bone marrow, as well as the isolation of extramedullary progression in the absence of the presence of myeloid disease. In the future, sequential MRD or molecular studies detected with MFC could help to disadvantage what grade of MRD is reached and whether further treatment is needed in clinical practice. However, the interpretation of MRD warrants caution as they are based on limited studies that can perhaps be relied on for MM typing or molecular subgroups, as well as therapeutic applications.