Pomalidomide
Pomalidomide (originally CC-4047 or 3-amino-thalidomide) is a derivative of thalidomide that is antiangiogenic and also acts as an immunomodulator. Pomalidomide, as the newest immunomodulatory agent (IMiD), has shown substantial in vitro antiproliferative
- PDF / 507,733 Bytes
- 14 Pages / 439.37 x 666.142 pts Page_size
- 51 Downloads / 150 Views
Abstract
Pomalidomide (originally CC-4047 or 3-amino-thalidomide) is a derivative of thalidomide that is antiangiogenic and also acts as an immunomodulator. Pomalidomide, as the newest immunomodulatory agent (IMiD), has shown substantial in vitro antiproliferative and proapoptotic effects. In vivo studies have suggested limited cross-resistance between lenalidomide and pomalidomide, and the response of pomalidomide in relapsed and refractory (RR) multiple myeloma (MM) patients, including those who are refractory to both lenalidomide and bortezomib, has induced notable enthusiasm. Several studies have evaluated continuous (2 mg/day) or alternate (5 mg/2 day) dose schedules of pomalidomide, as well as 2 versus 4 mg schedules, and pomalidomide alone versus in combination with dexamethasone or other antimyeloma agents. Since pomalidomide plus low-dose dexamethasone has shown better responses, progression-free and overall survival than high-dose dexamethasone or pomalidomide alone, subsequent trials investigating pomalidomide combination therapy have been initiated. Among these trials combinations with alkylating agents (cyclophosphamide, bendamustin), anthracyclins (pegylated liposomal doxorubicin), proteasome inhibitors (bortezomib, carfilzomib), and various others can be found. Pomalidomide has also been assessed in AL amyloidosis, MPNs (myelofibrosis [MF]), Waldenstrom’s macroglobulinemia, solid tumors (sarcoma, lung cancer), or HIV and—for AL amyloidosis and
M. Engelhardt (&) R. Wäsch H. Reinhardt M. Kleber Hematology and Oncology, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany e-mail: [email protected]
U. M. Martens (ed.), Small Molecules in Oncology, Recent Results in Cancer Research 201, DOI: 10.1007/978-3-642-54490-3_22, Springer-Verlag Berlin Heidelberg 2014
359
360
M. Engelhardt et al.
MF—has already proven remarkable activity. Due to its potency, pomalidomide was approved by the US Food and Drug Administration (FDA) for RRMM in 2/ 2013 and has also been approved by the European Medicines Agency (EMA).
Contents 1 Structure and Mechanism of Action................................................................................... 2 Preclinical Data ................................................................................................................... 3 Clinical Data........................................................................................................................ 4 MM ...................................................................................................................................... 5 AL Amyloidosis .................................................................................................................. 6 Myelofibrosis ....................................................................................................................... 7 Toxicity................................................................................................................................ 8 Drug Interactions ..
