The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients.

Despite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody–drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials and also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real-life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations.

In multiple myeloma impressive outcomes have improved with the introduction of new therapeutic approaches, mainly those including naked monoclonal antibodies such as daratumumab and isatuximab. However, moving to earlier lines of therapy with effective anti-myeloma drugs led to an increase in the number of patients who developed multi-refractoriness to them early on. Currently, triple- or multi-refractory MM represents an unmet medical need, and their management remains a complicated challenge. 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. Nevertheless, several issues regarding their use are unsolved, such as how to select patients for each strategy or how to sequence these therapies within the MM therapeutic landscape. Here we provide an overview of the most recent data about approved conjugated monoclonal antibody belantamab, mafodotin, bispecific antibody teclistamab, and other promising compounds under development, mainly focusing on the ongoing clinical trials with monoclonal antibody combination approaches in advanced and earlier phases of MM treatment.

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment. Moreover, he must deal not only with organ issues related to MM such as bone disease, renal failure or neurological disease but also with adverse events, often very serious, related to novel therapies, particularly new generation immunotherapies such as CAR T cell therapy and bispecific antibodies. In this review, we provide an overview on the newer MM diagnostic and monitoring strategies and on the main side effects of MM therapies, focusing on adverse events occurring during treatment with CAR T cells and bispecific antibodies.

Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and daratumumab, directed against CD38, in combination with Rd and with bortezomib and dexamethasone (Vd), have been approved for the treatment of relapsed/refractory MM (RRMM) after they demonstrated excellent efficacy. More recently, another anti-CD38 MoAb named isatuximab was approved by FDA in combination with pomalidomide-dexamethasone (Pd) in the same setting. Many phase II and III trials with regimens containing these MoAbs are ongoing, and when available, preliminary data are very encouraging. In this review we will describe the results of major clinical studies that have been conducted with elotuzumab, daratumumab and isatuximab in RRMM, focusing on phase III trials. Moreover, we will summarized the emerging MoAbs-based combinations in the RRMM landscape.

Background/Objectives: Treatments for multiple myeloma (MM) have expanded in the last decade, and the overall survival (OS) of MM patients (pts) is in continuous improvement. With the availability of new treatments and the use of high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation (ASCT), the median OS of newly diagnosed MM (NDMM) pts is 6–8 years. To date, approximately 50% and 28% of MM patients are still alive at 5 years and 10 years. Few data are reported concerning the characteristics of the long-term survival MM pts. Methods: the aim of this observational multicenter study is to analyze the clinical profile of MM pts who have survived 10 years or longer, to identify possible predictors of long-term survival. Conclusions: this is a real-life observation of a cohort of 344 long-term survivors with MM. The median age of the entire cohort was 59 years (range 27–83). The median years from diagnosis was 13.4 (range 11.3–16.3). Our analysis identified age more than 60 years, hypoalbuminemia at diagnosis, and a number of anti-myeloma therapies equal or more than 3 as significant independent prognostic factors for reduced OS. These finding underline the importance of designing prospective studies to identify clinical, biological, and molecular characteristics that could be used to better stratify newly diagnosed multiple myeloma pts in order to incorporate reproducible biomarkers and to identify tailored optimal target therapies.