Pomalidomide for multiple myeloma

Abstract

Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of 'novel agents': proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority - if not all - of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This drug profile focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low‐dose dexamethasone: A pooled analysis

“…Patients with relapsed and refractory multiple myeloma (RRMM) are usually older, have advanced disease, and may present with disease‐related comorbidities, such as myelosuppression, bone disease, or renal impairment, which may make further treatment and adverse event (AE) management difficult . Because of a high disease burden, lasting effects of prior treatment, and comorbidities, patients with RRMM are more susceptible to treatment‐related AEs than patients with newly diagnosed MM . This is in part due to exposure to multiple prior therapies, resulting in an increased risk for common treatment‐related AEs, including neutropenia, peripheral neuropathy, thrombocytopenia, anemia, and infection .…”

“…1-3 Because of a high disease burden, lasting effects of prior treatment, and comorbidities, patients with RRMM are more susceptible to treatment-related AEs than patients with newly diagnosed MM. [2][3][4][5][6] This is in part due to exposure to multiple prior therapies, resulting in an increased risk for common treatment-related AEs, including neutropenia, peripheral neuropathy, thrombocytopenia, anemia, and infection. 1-3,7-11 Infection is a particularly challenging treatment-emergent AE because it is a leading cause of morbidity and death in patients with RRMM.…”

A Novel Green Synthesis of Thalidomide and Analogs

“…However, recent studies prove that it is an effective immunomodulatory, antiangiogenic, and anticancer pharmaceutical [1,2]. This reemergence of thalidomide has led to a number of FDA approved derivatives including lenalidomide and pomalidomide (multiple myeloma) [3][4][5]. Currently thalidomide and its derivatives are used in the treatment of numerous diseases including Crohn [6][7][8], Leprosy [9][10][11], Graft-Versus-Host (GVHD) [12][13][14], and multiple forms of cancer [15][16][17].…”

Immunomodulatory drugs and their therapeutic effect in hematological malignancies through cereblon

“…Pomalidomide [4-Amino-2-(2,6-dioxopiperidin-3-yl) isoindole-1,3-dione] is a potent second-generation IMiD [27][28][29][30][31][32][33][34]. Pomalidomide has direct antiproliferative, pro-apoptotic, and antiangiogenic effects, as well as modulatory effects on bone resorption and on the immune system.…”