Compound Name:OprelvekinMolecular Target:Interleukin-11 receptorMolecular Structure:recombinant, human IL-11Licensed Indication:risk of, or pre-existing, severe thrombocytopenia and/or need for platelet transfusions following myelosuppressive chemotherapy in patients with nonmyeloid malignanciesManufacturer and/or Distributor:WyethInitial FDA Approval1997SummaryOprelvekin (Neumega) is recombinant human interleukin-11 (IL-11). It is produced in E. coli, and it differs from the native molecule by the absence of the amino-terminal proline residue and the lack of glycosylation. These alterations do not change its bioactivity, either in vitro or in vivo. IL-11 can stimulate the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induce megakaryocyte maturation, all of which results in increased platelet production. IL-11 can also interact with multiple other cell types, including other hematopoietic lineages, epithelial cells, osteoclasts, neurons, and adipose tissue. It induces acute phase reactants and fever, and it can modulate extracellular matrix metabolism. These multipotent activities may be responsible for some of the adverse reactions to oprelvekin, and have suggested additional therapeutic applications. Oprevlekin is administered once daily be subcutaneous injections for courses of 10-21 days beginning after completion of chemotherapy. In 1997, oprevlekin was approved for maintenance of platelets levels in adult patients who have nonmyeloid malignancies and who are at high risk of severe thrombocytopenia following myelosuppressive chemotherapy. Significant serious safety concerns are: (1) allergic reactions, including anaphylaxis; (2) fluid retention, including peripheral edema, pulmonary edema, capillary leak syndrome, exacerbation of pre-existing effusions and congestive heart failure; dilutional anemia; (3) cardiac arrhythmias (mainly atrial fibrilliation/flutter); (4) stroke; (5) papilledema; and (6) periosteal bone formation (manifesting as bone pain)References

Package Insert: http://www.pfizer.com/files/products/uspi_neumega.pdf

1. Wilde MI, Faulds D. Oprelvekin: a review of its pharmacology and therapeutic potential in chemotherapy-induced thrombocytopenia. BioDrugs. 1998 Aug;10(2):159-171. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18020592

2. Peterson DC, Inwards DJ, Younge BR. Oprelvekin-associated bilateral optic disk edema. Am J Ophthalmol. 2005 Feb;139(2):367-368. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15734010

3. Cantor SB, Elting LS, Hudson DV, Jr., Rubenstein EB. Pharmacoeconomic analysis of oprelvekin (recombinant human interleukin-11) for secondary prophylaxis of thrombocytopenia in solid tumor patients receiving chemotherapy. Cancer. 2003 Jun 15;97(12):3099-3106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12784347

4. Kaye JA. FDA licensure of NEUMEGA to prevent severe chemotherapy-induced thrombocytopenia. Stem Cells. 1998;16 Suppl 2:207-223. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11012193

5. Isaacs C, Robert NJ, Bailey FA, Schuster MW, Overmoyer B, Graham M, et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 1997 Nov;15(11):3368-3377. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9363868

6. Kurzrock R. rhIL-11 for the prevention of dose-limiting chemotherapy-induced thrombocytopenia. Oncology (Williston Park). 2000 Sep;14(9 Suppl 8):9-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11033833

7. Du X, Williams DA. Interleukin-11: review of molecular, cell biology, and clinical use. Blood. 1997 Jun 1;89(11):3897-3908. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9166826

8. Side effects of cytokines approved for therapy. Baldo BA. Drug Saf. 2014 Nov;37(11):921-43.