Immunotherapeutic strategies targeting B cell maturation antigen in multiple myeloma

Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen (BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease (MRD) negative patients, will also be discussed.

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma

“…Belantamab Mafodotin was first tested in both disseminated and subcutaneous human MM xenograft mouse models where it was shown to induce a complete eradication of the neoplasm without inducing weight loss of the mice, thus confirming the absence of toxicity (170). Subsequently, it was investigated in phase I (171) and phase II trials (160), with encouraging about 30% of overall response in penta-refractory patients and now is being tested in combination with lenalidomide and pomalidomide for patients with relapsed/refractory MM (143), as recently described in several recent comprehensive reviews (172)(173)(174)(175)(176)(177)(178)(179)(180). The most common grade 3-4 adverse events include: keratopathy (181,182), thrombocytopenia, and anemia (160).…”

BCMA in Multiple Myeloma—A Promising Key to Therapy

“…The purpose of manufacturing CD52-deficient T cells is to allow the application of alemtuzumab concurrently or prior to engineered T cells, which potentially eliminate CD52 expressing host T cells, to mediate engraftment and avoid allorejection [ 92 , 93 ]. Moreover, the safety of BCMA 1-R2 CAR-T cells is enhanced by the incorporation of intra-CAR rituximab binding domain as an off switch, enabling the elimination of CAR-T with rituximab [ 94 ].…”

Bispecific T Cell Engagers for the Treatment of Multiple Myeloma: Achievements and Challenges

“…The only exception are plasmacytoid dendritic cells which have been shown to help survival of MM in the bone marrow [62]. BCMA is a wildly popular drug target for antibody-drug conjugates, CAR-Ts, as well as BTCEs in MM [63].…”