title: The European medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: summary of the scientific assessment of the committee for medicinal products for human use.
abstract: On August 5, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pomalidomide in combination with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. Pomalidomide is an immunomodulating agent. The recommended starting dose of pomalidomide is 4 mg once daily taken on days 1-21 of repeated 28-day cycles. The main evidence of efficacy for pomalidomide in MM was based on a phase III multicenter, randomized, open-label study (CC-4047-MM-003) in which pomalidomide plus low-dose dexamethasone therapy (POM+LoDEX) was compared with high-dose dexamethasone alone (HiDEX) in previously treated adult patients with relapsed and refractory multiple myeloma who had received at least two prior treatment regimens, including both lenalidomide and bortezomib, and had demonstrated disease progression on the last therapy. For the intent-to-treat population, median progression-free survival based on International Myeloma Working Group criteria was 15.7 weeks (95% confidence interval [CI]: 13.0-20.1) in the POM+LoDEX group versus 8.0 weeks (95% CI: 7.0-9.0) in the HiDEX group (log-rank p value <.001). Overall survival (secondary endpoint) was also different in the two treatment groups (hazard ratio 0.53 [95% CI: 0.37-0.74]). The most commonly reported adverse reactions to pomalidomide in clinical studies were anemia (45.7%), neutropenia (45.3%) and thrombocytopenia (27%), fatigue (28.3%), pyrexia (21%), peripheral edema (13%), and infections including pneumonia (10.7%). Peripheral neuropathy adverse reactions were reported in 12.3% of patients, and venous embolic or thrombotic (VTE) adverse reactions were reported in 3.3% of patients. Pomalidomide is expected to be teratogenic. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia zahra.hanaizi@ema.europa.eu.
authors: Zahra
authors: Z
authors: Hanaizi
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Beatriz
authors: B
authors: Flores
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Robert
authors: R
authors: Hemmings
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Jorge
authors: J
authors: Camarero
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Arantxa
authors: A
authors: Sancho-Lopez
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Tomas
authors: T
authors: Salmonson
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Christian
authors: C
authors: Gisselbrecht
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Edward
authors: E
authors: Laane
authors: European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors: Francesco
authors: F
authors: Pignatti
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005060:Europe; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011719:Pyrazines / Q000008:administration & dosage; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; C467566:pomalidomide; D000077269:Lenalidomide
keywords: EMA; European Medicines Agency; Imnovid; Multiple myeloma; Pomalidomide