The recent approval of new immunotherapeutic approaches such as conjugated monoclonal antibodies, bispecific antibodies, and CAR T cells could be a turning point for these heavily pretreated patients. advanced and earlier phases of MM treatment. Keywords:relapsed multiple myeloma, bispecific antibodies, teclistamab, elranatamab, talquetamab, cevostamab == 1. Introduction == Multiple myeloma (MM) is a B-cell malignancy derived from an expansion of clonal plasma cells in the bone marrow, which produce monoclonal immunoglobulins (M-protein) that could settle down into vital organs, causing their progressive dysfunction, with the typical CRAB clinical MM manifestations such as osteolytic bone disease, anemia, or renal failure [1]. MM could be biologically described as a journey from a premalignant disorder known as Monoclonal Gammopathy of Undetermined Significance (MGUS), which develops from normal plasma cells via primary genetic events, through the smoldering/asymptomatic MM, until the active MM, which becomes clinically evident. Along this journey, secondary genetic events such as genetic abnormalities, epigenetic abnormalities, and cytogenetic abnormalities could take over, resulting in the genetic evolution of the disease and defining the prognosis of MM in terms of its resistance to drugs [2]. The dysregulation of the immune system is an important factor in MM pathogenesis. Thus, trials about drugs acting on the complex relationship between the immune system and the tumor cells could be considered really appealing. As a result, immunotherapy treatment approaches in MM have exponentially evolved over the last two decades. The graft-versus-myeloma effect of allogeneic hematopoietic cell transplantation paved the way for the rising potential role of immunotherapy for MM, having been shown to induce long-term remission and potential cure in a subset of MM patients with a great safety price to pay [3], which has limited its use in real life. First-generation proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs), bortezomib and thalidomide, respectively, could be considered two of the first available forms of immunotherapy that, replacing standard chemotherapy several years ago, became the backbone of MM treatments with a significant improvement in MM outcomes [4]. The development of second- and third-generation PIs (carfilzomib and ixazomib) and IMIDs (lenalidomide and pomalidomide) could be considered their first evolution, improving their safety profile and strengthening their efficacy [5]. Therefore, monoclonal antibodies (mAb), firstly licensed for RRMM and then also for NDMM settings, have even more improved outcomes in MM patients when administered alone or in association with other drugs [6]. MAbs could represent a basic form of immunotherapy, characterized by the infusion of target-specific antibodies produced from a Ace2 single clone capable of activating the immune system [7]. These drugs are mostly used in the MM treatment landscape in association, so clinical trials have recently demonstrated the superiority of triplets over duplets [8], quadruplets over triplets [9], Prasugrel (Effient) and so on in the near future. In the phase 2 MASTER trial [10], 123 NDMM patients received four cycles of daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) Prasugrel (Effient) as induction and autologous stem cell transplantation (ASCT), followed by 0, 4, and 8 cycles Prasugrel (Effient) of Dara-KRd consolidation according to MRD status assessed after induction, ASCT, and after the second cycle in each block of Dara-KRd consolidation. Patients with two consecutive MRD negatives discontinued therapy and transitioned to observation and MRD surveillance (MRD-SURE), while patients without two consecutive MRD negatives after consolidation underwent lenalidomide maintenance and MRD assessment Prasugrel (Effient) after 6 and 18 months. The primary endpoint of the study was reaching MRD of less than 105by NGS during treatment, and 81% of patients reached it. Seventy-one percent of patients had two consecutive MRD-negative assessments and entered MRD surveillance, with 52% of them remaining MRD-negative and off therapy [10]. Overall, 2-year PFS was 87% and 2-year OS was 94% [11]. Despite recent advances in outcomes due to the benefits given by novel therapeutic strategies, MM remains incurable, and some disease subgroups continue to not.