ICD-10 Specific code C90: Multiple myeloma and malignant plasma cell neoplasms

Bendamustine is an alkylating antitumour agent with unique activity. The antineoplastic and cytocidal effect of bendamustine is based essentially on a cross-linking of DNA single and double strands by alkylation. As a result, DNA matrix functions and DNA synthesis and repair are impaired.

Bortezomib is a proteasome inhibitor. It is specifically designed to inhibit the chymotrypsin-like activity of the 26S proteasome in mammalian cells. Inhibition of the 26S proteasome prevents this targeted proteolysis and affects multiple signalling cascades within the cell, ultimately resulting in cancer cell death.

Chlorambucil is an aromatic nitrogen mustard derivative which acts as a bifunctional alkylating agent. In addition to interference with DNA replication, chlorambucil induces cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation of an apoptosis promoter.

Cyclophosphamide has been demonstrated to have a cytostatic effect in many tumour types. The active metabolites of cyclophosphamide are alkylating agents which transfer alkyl groups to DNA during the process of cell division, thus preventing normal synthesis of DNA.

Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds to the CD38 protein expressed at a high level on the surface of multiple myeloma tumour cells, as well as other cell types and tissues at various levels. CD38 protein has multiple functions such as receptor mediated adhesion, signalling and enzymatic activity. Daratumumab has been shown to potently inhibit the in vivo growth of CD38-expressing tumour cells.

Dexamethasone is a synthetic glucocorticoid; it combines high anti-inflammatory effects with low mineralocorticoid activity. It has an approximately 7 times greater anti-inflammatory potency than prednisolone, another commonly prescribed corticosteroid. At high doses it reduces the immune response.

Elotuzumab is an immunostimulatory humanised, IgG1 monoclonal antibody that specifically targets the SLAMF7 (signaling lymphocyte activation molecule family member 7) protein. Elotuzumab directly activates natural killer cells through both the SLAMF7 pathway and Fc receptors enhancing anti-myeloma activity in vitro. Elotuzumab also targets SLAMF7 on myeloma cells and through interactions with Fc receptors on specific immune cells, promotes the killing of myeloma cells through NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and macrophage-mediated antibody-dependant cellular phagocytosis (ADCP).

The main effect of etoposide appears to be at the late S and early G₂ portion of the cell cycle in mammalian cells. The predominant macromolecular effect of etoposide seems to be the rupture of the double strand by an interaction with DNA-topoisomerase II or by the formation of free radicals. Etoposide has been shown to cause metaphase arrest in chick fibroblasts.

Ifosfamide is an antineoplastic, a cytotoxic alkylating agent. It is a prodrug and shows no in vitro cytotoxic activity until activated by microsomal enzymes. The cytotoxic activity of ifosfamide (alkylation of the nucleophilic centres in the cells) is associated with the activated oxazaphosphorine ring hydroxylated at the C4 atom which interacts with DNA-DNA cross linking. This activity manifests itself by blocking the late S and early G2 phases of the cell cycle.

Recombinant interferon alfa-2b is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA techniques. Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant immunomodulatory activity in vitro.

Lenalidomide binds directly to cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex that includes deoxyribonucleic acid (DNA) damage-binding protein 1(DDB1), cullin 4 (CUL4), and regulator of cullins 1 (Roc1). Specifically, lenalidomide inhibits proliferation and enhances apoptosis of certain haematopoietic tumour cells (including MM plasma tumour cells, follicular lymphoma tumour cells and those with deletions of chromosome 5), enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number of NK, T and NK T cells. The lenalidomide mechanism of action also includes additional activities such as anti-angiogenic and proerythropoietic properties.

Methylprednisolone is a synthetic glucocorticoid and a methyl derivative of prednisolone. Methylprednisolone is a potent anti-inflammatory agent with the capacity to profoundly inhibit the immune system.

Panobinostat is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs at nanomolar concentrations. HDACs catalyse the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation.

Prednisolone is a glucocorticoid which has anti-inflammatory activity. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.

Teclistamab is a full-size, IgG4-PAA bispecific antibody that targets the CD3 receptor expressed on the surface of T cells and B cell maturation antigen (BCMA), which is expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. With its dual binding sites, teclistamab is able to draw CD3+ T cells in close proximity to BCMA+ cells, resulting in T cell activation and subsequent lysis and death of BCMA+ cells, which is mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells.