title: Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation.
abstract: We previously reported that daily dose pomalidomide (CC-4047), a thalidomide analogue, has excellent anti-myeloma activity but is associated with myelosuppression and deep vein thrombosis. We report here a phase 1 study to determine the maximum tolerated dose (MTD) of pomalidomide at 1 mg, 2 mg, 5 mg and 10 mg on alternate days (ad). Twenty patients with relapsed myeloma were treated. Grade 4 neutropenia occurred in all patients receiving 10 mg and the MTD was defined as 5 mg ad. No thrombotic events were observed. Pomalidomide was continued following the 4-week MTD study in 17/20 patients for a median of 14 months. 10% of patients had a complete response and >50% reduction in paraprotein was achieved in 50% of subjects. Progression-free survival was 10.5 months and median overall survival was 33 months. A significant rise was observed in the proportion of CD8(+) cells. Alternate day pomalidomide was associated with a marked reduction in the incidence of thrombosis whilst maintaining excellent anti-myeloma activity. This trial provides further in vivo evidence that pomalidomide modulates the immune system in myeloma patients. Phase 2 studies to further assess the optimal schedule of administration and anti-myeloma activity of this agent are planned.
authors.affiliation: Department of Haematology, Guys Hospital, Guys and St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Streetly
authors.forename: Kylie
authors.initials: K
authors.lastname: Gyertson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Daniel
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: Majid
authors.initials: M
authors.lastname: Kazmi
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Schey
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001772:Blood Cell Count; D003907:Dexamethasone / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D013792:Thalidomide; D003907:Dexamethasone; C467566:pomalidomide