Pharmacokinetic drug evaluation of ixazomib citrate for the treatment of multiple myeloma.

multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors. Areas covered: ixazomib is the first oral PI recently approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA) in combination with lenalidomide and dexamethasone as salvage therapy in MM patients.

Melphalan hydrochloride for the treatment of multiple myeloma.

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.

Minimal residual disease after transplantation or lenalidomide-based consolidation in myeloma patients: a prospective analysis.

We analyzed 50 patients who achieved at least a very good partial response in the RV-MM-EMN-441 study. Patients received consolidation with autologous stem-cell transplantation (ASCT) or cyclophosphamide-lenalidomide-dexamethasone (CRD), followed by Lenalidomide-based maintenance. We assessed minimal residual disease (MRD) by multi-parameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) after consolidation, after 3 and 6 courses of maintenance, and thereafter every 6 months until progression.

Association of RAMP1 rs7590387 with the risk of migraine transformation into medication overuse headache.

Objectives/background: We herein investigated the role of polymorphisms in calcitonin gene-related peptide (CGRP)-related genes looking at the association of rs3781719 (T > C) in the calcitonin gene-related polypeptide-alpha (CALCA) gene and of rs3754701 (T > A) and rs7590387 (C > G) at the receptor activity modifying 1 (RAMP1) locus with triptan response in patients with migraine without aura (MwoA). In addition, their role was evaluated as risk factors for transformation of episodic migraine into medication overuse headache (MOH). The CGRP has a central role in the pathogenesis of migraine; however, little information is currently available concerning the role of polymorphisms in CGRP-related genes as determinants of clinical response to anti-migraine drugs or as risk factors for migraine chronification.

Pharmacophore modeling technique applied for the discovery of proteasome inhibitors.

Introduction: The 26S proteasome has many important roles in the biological functions of the cells, and proteasome inhibitors have multiple and complex activities on cells. These compounds can be natural or synthesized. Most synthetic derivatives have been rationally designed, synthesized and optimized to obtain the best selectivity and increase the activity.

Pomalidomide for the treatment of relapsed-refractory multiple myeloma: a review of biological and clinical data.

Despite the improvements thanks to the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs), nearly all myeloma patients eventually become refractory to these drugs. Consequently, the outcome of these patients is very poor. Pomalidomide is a new IMiD with a similar structure to the commonly used IMiD thalidomide and lenalidomide.

The mechanism of action, pharmacokinetics, and clinical efficacy of carfilzomib for the treatment of multiple myeloma.

Introduction: The development of novel agents, such as immunomodulatory drugs and proteasome inhibitors, has led to a considerable increment in the response rate (RR) and outcomes for multiple myeloma (MM) patients. Unfortunately, MM patients will inevitably relapse and become resistant to new drugs. This led to the continuous development of novel agents.

Evaluation of the pharmacokinetics, preclinical, and clinical efficacy of lenalidomide for the treatment of multiple myeloma.

Introduction: Lenalidomide is an oral immunomodulatory drug, which was recently introduced for the treatment of multiple myeloma (MM). It has been used for the treatment of newly diagnosed and relapsed MM patients, as both maintenance and preventive therapy. Available data show a progression-free survival and overall survival improvement associated with this drug.