Diagnostic and therapeutic challenges in the management of intermediate and frail elderly multiple myeloma patients

Multiple myeloma (MM) mostly affects elderly patients, which represent a highly heterogeneous population. Indeed, comorbidities, frailty status and functional reserve may vary considerably among patients with similar chronological age. For this reason, the choice of treatment goals and intensity is particularly challenging in elderly patients, and it requires a multidimensional evaluation of the patients and the disease. In recent years, different tools to detect patient frailty have been developed, and the International Myeloma Working Group frailty score currently represents the gold standard. It identifies intermediate-fit and frail patients requiring gentler treatment approaches compared to fit patients, aiming to preserve quality of life and prevent toxicities. This subset of patients is underrepresented in clinical trials, and studies exploring frailty-adapted approaches are scarce, making the choice of therapy extremely challenging. Treatment options for intermediate-fit and frail patients might include dose-adapted combinations, doublets, and less toxic combinations based on novel agents. This review analyzes the available tools for the assessment of frailty and possible strategies to improve the discriminative power of the scores and expand their use in real-life and clinical trial settings. Moreover, it addresses the main therapeutic challenges in the management of intermediate-fit and frail MM patients at diagnosis and at relapse

Investigation on the effect of the gas-to-metal ratio on powder properties and PBF-LB/M processability

Metal powders for the laser powder bed fusion process are usually produced via gas atomization. However, due to the tight particle size distribution required for this application, the yield of the atomization process is low, resulting in a high-powder cost. In this work, atomization process parameters were varied to increase the gas-to-metal ratio to reduce the particle size distribution produced, and therefore increase the yield of the process. As a result, eight powders were produced starting from scrap AISI 136L material at different gas-to-metal ratio values, and the atomization process yield was successfully increased by 50%. First, the eight powders were characterized in terms of powder size, shape distributions, and flowability. Later, all powders were used to produce tensile specimens. The powders produced at higher yield exhibited a larger number of fine particles but slightly lower circularity, particularly in the coarse fraction. Furthermore, powders produced at a high gas-to-metal ratio demonstrated enhanced flowing properties and higher packing density. Consequently, these powders exhibited superior tensile performance, with ultimate tensile strength (UTS) ranging from 651 to 673 MPa and elongation values between 63 and 66%

Monoclonal antibodies to treat multiple myeloma: A dream come true

Immunotherapy is increasingly used in the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) are safe and effective ways to elicit immunotherapeutic responses. In 2015, daratumumab has become the first mAb approved by the Food and Drug Administration for clinical use in MM and, in the last 5 years, a lot of clinical and preclinical research has been done to optimize the use of this drug class. Currently, mAbs have already become part of standard-of-care combinations for the treatment of relapsed/refractory MM and very soon they will also be used in the frontline setting. The success of simple mAbs (‘naked mAbs’) prompted the development of new types of molecules. Antibody–drug conjugates (ADCs) are tumor-targeting mAbs that release a cytotoxic payload into the tumor cells upon antigen binding in order to destroy them. Bispecific antibodies (BiAbs) are mAbs simultaneously targeting a tumor-associated antigen and an immune cell-associated antigen in order to redirect the immune cell cytotoxicity against the tumor cell. These different constructs produced solid preclinical data and promising clinical data in phase I/II trials. The aim of this review article is to summarize all the recent developments in the field, including data on naked mAbs, ADCs and BiAbs

Therapeutic monoclonal antibodies and antibody products: Current practices and development in multiple myeloma

Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs®), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation