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El mieloma múltiple es una enfermedad neoplásica que constituye aproximadamente el 10% de todos los tumores hematológicos y el 1,8% de todas las neoplasias. Se caracteriza por la proliferación clonal de células plasmáticas patológicas, acumuladas principalmente en MO, enfermedad lítica ósea y una severa inmunosupresión, sobre todo en etapas avanzadas de la enfermedad. A pesar de los avances en el tratamiento del mieloma en la última década, el MM sigue siendo una enfermedad incurable, donde la mayoría de pacientes recaen con periodos de respuesta cada vez más cortos. Por esta razón, existe la necesidad de encontrar nuevas opciones terapéuticas basadas en distintos mecanismos de acción para superar este escenario de recaídas y refractariedad a los tratamientos actuales.La terapia T CAR autóloga es una terapia innovadora que ha logrado resultados impresionantes en neoplasias de células B, incluido MM/RR, que ha llevado a la aprobación de dos productos en el mercado. La experiencia con células T CAR comerciales revelan limitaciones como toxicidades graves, producción larga y costosa, y con un control de la enfermedad subóptimo en muchos pacientes. Por otra parte, pacientes que recaen a las terapias aprobadas T CAR BCMA no tienen muchas más opciones terapéuticas. Por tanto, se requieren estrategias alternativas o secuenciales a las terapias T CAR BCMA. Las células NK-CAR emergen como un abordaje terapéutico a menor coste y mucho más seguro, sin generar EICH, citopenias prolongadas, CRS o neurotoxicidades graves..., Multiple myeloma is a neoplastic disease that constitutes approximately 10% of all hematologic tumors and 1.8% of all neoplasms. It is characterized by clonal disease of pathological plasma cells, accumulated mainly in bone marrow, lytic bone lesions, and severe immunosuppression, especially in advanced stages of the disease. Despite advances in the treatment of myeloma in the last decade, MM remains incurable, where most patients relapse with increasingly shorter response periods. For this reason, there is an unmet need to find new therapeutic options based on different mechanisms of action to overcome this scenario of relapses and refractoriness to current treatments.Autologous CAR T therapy is an innovative therapy that has achieved impressive results in B-cell neoplasms, including RR/MM, leading to the approval of two products on the market. Experience with commercial CAR T cells reveals limitations such as severe toxicities, time-consuming and expensive production, and suboptimal disease control in many patients. On the other hand, patients receiving the approved BCMA CAR T therapies do not have many other therapeutic options. Therefore, alternative or sequential strategies to BCMA CAR T therapies are required. CAR NK cells are emerging as a lower cost and much safer therapeutic approach, without generating GVHD, prolonged cytopenias, CRS or severe neurotoxicity...

Multiple myeloma (MM) is a hematologic cancer characterized by clonal proliferation of plasma cells in the bone marrow (BM). The progression, from the early stages of the disease as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM and occasionally extramedullary disease, is drastically affected by the tumor microenvironment (TME). Soluble factors and direct cell–cell interactions regulate MM plasma cell trafficking and homing to the BM niche. Mesenchymal stromal cells, osteoclasts, osteoblasts, myeloid and lymphoid cells present in the BM create a unique milieu that favors MM plasma cell immune evasion and promotes disease progression. Moreover, TME is implicated in malignant cell protection against anti-tumor therapy. This review describes the main cellular and non-cellular components located in the BM, which condition the immunosuppressive environment and lead the MM establishment and progression., Ministerio de Ciencia e Innovación (MICINN), Instituto de Salud Carlos III/ CRIS Foundation, Instituto de Salud Carlos III (ISCIII), Research Institute Hospital 12 de Octubre, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Multiple myeloma (MM) is a hematologic cancer characterized by clonal proliferation of plasma cells in the bone marrow (BM). The progression, from the early stages of the disease as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM and occasionally extramedullary disease, is drastically affected by the tumor microenvironment (TME). Soluble factors and direct cell–cell interactions regulate MM plasma cell trafficking and homing to the BM niche. Mesenchymal stromal cells, osteoclasts, osteoblasts, myeloid and lymphoid cells present in the BM create a unique milieu that favors MM plasma cell immune evasion and promotes disease progression. Moreover, TME is implicated in malignant cell protection against anti-tumor therapy. This review describes the main cellular and non-cellular components located in the BM, which condition the immunosuppressive environment and lead the MM establishment and progression.