Panminerva medica
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Multiple myeloma (MM) represents the second-most common hematologic malignancy. In the 1980s, induction therapy with alkylating agents, such as anthracyclines and steroids, as well as high-dose chemotherapy followed by autologous stem cell transplantation were the main therapeutic approaches for MM. Since the introduction of more effective drugs, such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies and histone deacetylase inhibitor, the new therapeutic algorithm allows of achieving a significantly improvement of prognosis. ⋯ Also, this is particular true in specific situations, such as extramedullary manifestations, in which tumor mass reduction becomes an urgent clinical need, or in case of chemotherapy-induced stem-cell mobilization. Moreover, melphalan represents the gold standard conditioning regimen since 2002, either alone or, possibly in the next future, in combination with busulfan. Finally, new chemotherapeutic agents with new mechanisms of action, such as melflufen, are in early experimental phase.
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Multiple myeloma (MM) is a hematological malignancy in which patients present with bone marrow infiltration of clonal terminally-differentiated plasma cells. Monoclonal protein in the serum and/or urine is frequently detected. Over the past decade, important progress has been made in the comprehension of disease biology and treatment personalization. Much work has been put into the development of chimeric antigen receptor (CAR) gene-modified T-cell therapy thought to be a promising therapeutic option for pluritreated patients with refractory MM. ⋯ Targeting an appropriate antigen(s) is the key to both safety and efficacy of CAR T approaches in MM as there is dearth of tumor-specific antigens. Most antigens tested are merely enriched on MM cells. Working with tumor-enriched antigens requires careful assessment of the balance between harm (toxicity) and benefit (disease eradication) to the patient. This review provides an up-to-date overview of the avenues that are being explored.
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Recent advances in treatment modalities have led to improved survival in patients with multiple myeloma (MM). However, despite these, MM remains an incurable disease. Many MM patients relapse through and become refractory to current treatment strategies or are intolerant due to toxicities arising from therapy. ⋯ Given the high expression of BCMA in malignant Plasma cells compared to those from normal healthy volunteers, targeting BCMA should reduce risks of on-target off-tumor toxicities. The main BCMA-targeting approaches currently used for treatment of MM include: 1) chimeric antigen receptor (CAR) T-cell therapy; 2) bi- and multi- specific antibodies; and 3) monoclonal antibodies and their drug conjugates. This review will outline these therapeutic agents and present their emerging clinical data.