title: Phase II study of pegylated liposomal doxorubicin, low-dose dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma.
abstract: Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma showed an overall response rate of 75%, with 29% achieving ≥ VGPR. Here, we investigated this combination (PLD 30 or 40 mg/m(2) intravenously, day 1; dexamethasone 40 mg orally, days 1-4; lenalidomide 25 mg orally, days 1-21; administered every 28 days) in a phase II study in patients with newly diagnosed symptomatic multiple myeloma to determine its efficacy and tolerability (ClinicalTrials.gov NCT00617591). At best response, patients could proceed with high-dose melphalan or with maintenance lenalidomide and dexamethasone. In 57 patients, we found that the overall response rate and rate of very good partial response and better on intent-to-treat, our primary endpoints, were 77.2% and 42.1%, respectively, with responses per the International Myeloma Working Group. Median progression-free survival was 28 months (95% CI 18.1-34.8), with 1- and 2-year overall survival rates of 98.1 and 79.6%. During induction, grade 3/4 toxicities were neutropenia (49.1%), anemia (15.8%), thrombocytopenia (7%), fatigue (14%), febrile neutropenia (8.8%), and venous thromboembolic events (8.8%). During maintenance, grade 3/4 toxicities were mainly hematologic. We found this combination to be active in patients with newly diagnosed myeloma, with results comparable to other lenalidomide-based induction strategies without proteasome inhibition. In addition, maintenance therapy with lenalidomide was well tolerated.
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Rachid C
authors.initials: RC
authors.lastname: Baz
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Shain
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Hussein
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sullivan
authors.forename: Elizabeth Finley
authors.initials: EF
authors.lastname: Oliver
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Nardelli
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Nodzon
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhao
authors.forename: Jose Leonel
authors.initials: JL
authors.lastname: Ochoa-Bayona
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.forename: William S
authors.initials: WS
authors.lastname: Dalton
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012074:Remission Induction; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D013792:Thalidomide; D003907:Dexamethasone; D004317:Doxorubicin; D000077269:Lenalidomide
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