title: Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma.
abstract: Pomalidomide and low-dose dexamethasone (PomDex) is standard treatment of lenalidomide refractory myeloma patients who have received >2 prior therapies. We aimed to assess the safety and efficacy of the addition of oral weekly cyclophosphamide to standard PomDex. We first performed a dose escalation phase 1 study to determine the recommended phase 2 dose of cyclophosphamide in combination with PomDex (arm A). A randomized, multicenter phase 2 study followed, enrolling patients with lenalidomide refractory myeloma. Patients were randomized (1:1) to receive pomalidomide 4 mg on days 1 to 21 of a 28-day cycle in combination with weekly dexamethasone (arm B) or pomalidomide, dexamethasone, and cyclophosphamide (PomCyDex) 400 mg orally on days 1, 8, and 15 (arm C). The primary end point was overall response rate (ORR). Eighty patients were enrolled (10 in phase 1 and 70 randomized in phase 2: 36 to arm B and 34 to arm C). The ORR was 38.9% (95% confidence interval [CI], 23-54.8%) and 64.7% (95% CI, 48.6-80.8%) for arms B and C, respectively (P = .035). As of June 2015, 62 of the 70 randomized patients had progressed. The median progression-free survival (PFS) was 4.4 (95% CI, 2.3-5.7) and 9.5 months (95% CI, 4.6-14) for arms B and C, respectively (P = .106). Toxicity was predominantly hematologic in nature but was not statistically higher in arm C. The combination of PomCyDex results in a superior ORR and PFS compared with PomDex in patients with lenalidomide refractory multiple myeloma. The trial was registered at www.clinicaltrials.gov as #NCT01432600.
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Rachid C
authors.initials: RC
authors.lastname: Baz
authors.affiliation: Myeloma Program, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA;
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Martin
authors.affiliation: Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Shain
authors.affiliation: Multiple Myeloma Program, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY; and.
authors.forename: Hearn J
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Myeloma Program, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA;
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wolf
authors.affiliation: Myeloma Program, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA;
authors.forename: Anuj
authors.initials: A
authors.lastname: Mahindra
authors.affiliation: Multiple Myeloma Program, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY; and.
authors.forename: Ajai
authors.initials: A
authors.lastname: Chari
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sullivan
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Nardelli
authors.affiliation: Multiple Myeloma Program, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY; and.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lau
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.affiliation: Multiple Myeloma Program, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY; and.
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide; C467566:pomalidomide