biological treatment options of multiple myeloma

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Multiple myeloma encompasses 10% of hematological malignancies and is characterised by end organ damage and the presence of bone lesions. Currently, myeloma therapies involve the use of combinations of multiple agents from various classes. These include proteosome inhibitors, monoclonal antibodies, Chimeric antigen receptor T cells, T cell engaging bispecific antibodies, antibody-drug conjugates along with steroids, and immunomodulatory therapies. Bortezomib, Carfilzomib, and Ixazomib are examples of proteasome inhibitors. Bortezomib is the predominant choice in treatment regimens. The basic action of proteosome inhibitors is to inhibit the degradation of proteins within the cell nucleus leading to the accumulation of proteins within the endoplasmic reticulum, The build up of folded and unfolded proteins eventually triggers apoptosis. Monoclonal antibodies are available in various forms that specifically target particular cell receptors. Daratumumab is a therapy that targets CD38, the primary receptor found on normal plasma cells and multiple myeloma cells. Alternatively, another potential target on the surface of cells is SLAMF7, sometimes referred to as CS1, which is specifically recognized by Elotuzumab. Both kinds of medications, protease inhibitors (PIs) and monoclonal antibodies, demonstrate significant effectiveness when taken in conjunction with other treatments or when combined. Chimeric antigen receptor T cell therapy, specifically ide-cel and cilta-cel, is an advanced treatment that improves the long-term survival of patients with recurring illnesses. Nevertheless, both medications exhibited inconsistent outcomes alongside elevated levels of toxicity and side effects. Engineered bispecific antibodies, which can bind to both malignant plasma cells and immune effector cells such as T cells and Natural killer cells, have demonstrated longer lasting redirection of T cells in vivo when compared to CAR T cells. Unlike CAR T cells, which lose their effectiveness within the initial months of administration. The last mode of therapy that specifically targets B cell membrane antigens combined with a chemotherapeutic drug is an Antibody-Drug conjugate; Belantamab mafadotin gained approval which was withdrawn afterwards when the progression-free survival of the drug was compared to pomalidomide/dexamethasone regimen. As a result, the initial therapy used currently as an ultimate treatment to treat multiple myeloma is a combination of three drugs which includes two modern therapies along with a weekly dose of dexamethasone. It was also shown that quadruplet treatment including an anti CD38 antibody, a proteosome inhibitor, an immunomodulator, and dexamethasone showed better response rates, longer periods of free disease progression, and enhancement of long term survival compared to triplet therapies. The choice of second-line therapy for recurrent disease is determined by the duration of the relapse and the medications used for the initial treatment. 35 Early relapses are treated with a combination of an anti-CD38 antibody and an immunomodulator or carfilzomib, along with weekly dexamethasone treatment. On the other hand, late relapses are treated by using previously used treatments in new combinations with agents like CAR T cells, selinexor, and bispecific antibodies. Ultimately, a common therapeutic approach is Autologous stem cell transplantation which has demonstrated comparable long term outcomes whether used in the first or second line of therapies.

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biological, treatment, multiple, myeloma
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