Melphalan hydrochloride for the treatment of multiple myeloma

Abstract

Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation and overproduction of monoclonal paraprotein, hypercalcemia, renal failure, anemia, osteolytic bone lesions, and infections. Melphalan, a nitrogen mustard, is an alkylating agent synthesized in 1953, and it has been used in multiple myeloma therapy for fifty years. Although novel agents have been introduced in the past few decades improving prognosis of the disease, melphalan still maintains a crucial role in the treatment of MM acting both as cytotoxic agent through damage to DNA, and as immunostimulatory drug by inhibiting Interleukin-6, as well as interaction with dendritic cells, and immunogenic effects in tumor microenvironment. Areas covered: This review focuses on available data about melphalan pharmacology and its role in clinical practice. Expert opinion: Melphalan remains crucial in therapy of multiple myeloma because of its good manageability, safety profile, efficacy, and economic sustainability. These characteristics make it pivotal also for new regimens in combination with novel agents.

Prediction and prognostic significance of BCAR3 expression in patients with multiple myeloma

“…For MM patients with age less than 65 years, high-dose treatment with autologous stem cells is a first-line effective treatment [31]. But MM is a kind of incurable disease and a B-cell differentiated tumor, whose character is cloned plasma cell proliferations, kidney failure, anemia, dissolve the bony lesions, hypercalcemia and infection [32–34]. Free monoclonal immunoglobulins in serum or urine were found to be related with malignant plasma cell marrow infiltration [35, 36].…”

Cooling of the oral mucosa to prevent adverse effects of chemotherapeutic agents: An in vitro study

“…An example of other chemotherapeutic agents that could have been used and evaluated in this study is Melphalan, a bifunctional alkylating agent that does not require metabolic activation. Similar to 5‐FU, it incorporates into macromolecules, but instead Melphalan exerts its effects through DNA interstrand cross‐linking, which leads to replication arrest and cell death …”

Sinusoidal Obstruction Syndrome (SOS) in Multiple Myeloma with Renal Failure

“…Although melphalan is eliminated from plasma primarily by chemical hydrolysis to noncytotoxic monohydroxy and dihydroxy metabolites [29], it is both secreted and reabsorbed by the renal tubules. Therefore, its clearance is renal-function dependent [2]. For high-dose melphalan (200 mg/m 2 ), a reduced dose of 140 mg/m 2 is used when the creatinine clearance is less than 60 ml/min [30].…”

“…Although case 3 did not have a HSCT, he was exposed to prolonged periods of alkylating agents and antibiotics such as vancomycin in the setting of a serious infection and renal dysfunction which are all underlying risk factors (Table 2). Patients with renal failure are at a greater than normal risk of developing drug-induced SOS because of altered pharmacokinetics, with marked interindividual variation [2].…”