title: Superior overall survival of patients with myeloma achieving very good partial response or better to initial treatment with bortezomib, pegylated liposomal doxorubicin, and dexamethasone, predicted after two cycles by a free light chain- and M-protein-based model: extended follow-up of a phase II trial.
abstract: In myeloma, achievement of very good partial response (VGPR) post-transplant is associated with prolonged overall (OS) and progression-free survival (PFS). In this study of bortezomib, pegylated liposomal doxorubicin, and dexamethasone (VDD) in 40 patients with newly diagnosed myeloma (median follow-up 45.1 months), 2-/4-year OS estimates were 95.7%/86.5% versus 82.4%/58.2% for patients achieving ≥VGPR versus <VGPR to VDD (p=0.0241). In 30 patients undergoing transplant, PFS (p = 0.0357) and OS (p = 0.0272) were longer in patients achieving ≥VGPR to VDD. Achievement of ≥VGPR was predicted by a novel model based on occurrence after two cycles of ≥90% involved free light chain reduction, free light kappa/lambda ratio normalization, and/or ≥90% M-protein reduction. Prediction of ≥VGPR was associated with superior PFS and OS in patients with transplant. These findings emphasize the importance of achieving ≥VGPR to initial therapy, associated with prolonged OS. The predictive model provides a potential basis for developing individualized therapy, which requires further study.
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI 48109-5936, USA.
authors.forename: Dominik
authors.initials: D
authors.lastname: Dytfeld
authors.forename: Kent A
authors.initials: KA
authors.lastname: Griffith
authors.forename: Judah
authors.initials: J
authors.lastname: Friedman
authors.forename: Daniel
authors.initials: D
authors.lastname: Lebovic
authors.forename: Colleen
authors.initials: C
authors.lastname: Harvey
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Jakubowiak
mesh_terms: 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; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood; D015233:Models, Statistical; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D009194:Myeloma Proteins / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D007147:Immunoglobulin Light Chains; D009194:Myeloma Proteins; D011719:Pyrazines; C506643:liposomal doxorubicin; C085016:multiple myeloma M-proteins; D011092:Polyethylene Glycols; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin