title: A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma.
abstract: Our previous studies have shown that lowering the dose of pegylated liposomal doxorubicin (PLD) and bortezomib in combination with intravenous dexamethasone on a longer 4-week cycle maintained efficacy and improved tolerability in both previously untreated and relapsed/refractory (R/R) multiple myeloma (MM) patients. Lenalidomide has shown efficacy in combination with bortezomib and dexamethasone but this combination has been poorly tolerated. We conducted this phase 2 study (clinicaltrials.gov identifier: NCT01160484) to evaluate whether a longer 4-week schedule using modified doses and schedules of IV dexamethasone (40 mg), bortezomib (1.0 mg/m(2)) and PLD (4.0 mg/m(2)) administered on days 1, 4, 8, and 11 with lenalidomide 10 mg daily on days 1-14 (DVD-R) would be effective and tolerated for patients with R/R MM. A total of 40 heavily pretreated patients were enrolled and 84.6% showed clinical benefit (complete response, 20.5%; very good partial response, 10.3%; partial response, 17.9%; minimal response, 35.9%) to the combination regimen. An additional 10.3% showed stable disease and 5.1% progressed while on study. The regimen was well tolerated, with a low incidence of adverse events such as fatigue (40%), thrombocytopenia (35%), neutropenia (35%), anemia (30%), peripheral neuropathy (25%) and pneumonia (15%). Thus, the DVD-R regimen is well tolerated and produces high response rates for patients with R/R MM.
authors.affiliation: Oncotherapeutics, West Hollywood, CA 90069, USA. jberenson@imbcr.org
authors.forename: J R
authors.initials: JR
authors.lastname: Berenson
authors.forename: O
authors.initials: O
authors.lastname: Yellin
authors.forename: T
authors.initials: T
authors.lastname: Kazamel
authors.forename: J D
authors.initials: JD
authors.lastname: Hilger
authors.forename: C-S
authors.initials: CS
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Cartmell
authors.forename: T
authors.initials: T
authors.lastname: Woliver
authors.forename: M
authors.initials: M
authors.lastname: Flam
authors.forename: E
authors.initials: E
authors.lastname: Bravin
authors.forename: Y
authors.initials: Y
authors.lastname: Nassir
authors.forename: R
authors.initials: R
authors.lastname: Vescio
authors.forename: R A
authors.initials: RA
authors.lastname: Swift
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D000077269:Lenalidomide