title: Evolving therapeutic paradigms for multiple myeloma: back to the future.
abstract: Multiple myeloma (MM) is an ancient disease, but until the alkylating agent melphalan was found to have anti-myeloma properties in the 1950s there was virtually no effective therapy. By the late 1960s, extended dosing with melphalan and prednisone tripled survival from diagnosis and became the standard of care for newly diagnosed MM. "Maintenance therapy" to prolong survival through sustained disease control following induction chemotherapy was sought by 1970, but early strategies were ineffective and toxic. Subsequent applications of high-dose therapy (HDT)/autologous stem cell transplant (ASCT) changed the treatment paradigm for MM from extended dosing to an intensive strategy designed to eradicate the malignant cells in a single course of treatment. Although HDT-ASCT resulted in prolonged duration of remission and improved survival, the vast majority of patients still relapsed. Interferon (IFN) and glucocorticoid maintenance therapies demonstrated marginal improvements in outcomes but significant adverse effects. Novel agents introduced over the last decade have prolonged survival when given for maintenance following HDT-ASCT, but have also challenged the HDT-ASCT paradigm by achieving comparable remission rates when used alone as extended frontline therapy. This article reviews the evolution of therapeutic strategies for MM and discusses future questions facing MM investigators.
authors.affiliation: Multiple Myeloma Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Cherry
authors.forename: Neha
authors.initials: N
authors.lastname: Korde
authors.forename: Mary
authors.initials: M
authors.lastname: Kwok
authors.forename: Mark
authors.initials: M
authors.lastname: Roschewski
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods / Q000639:trends; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007372:Interferons / Q000008:administration & dosage; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D005938:Glucocorticoids; D007372:Interferons; D008558:Melphalan; D011241:Prednisone