title: Long-term outcomes of previously untreated myeloma patients: responses to induction chemotherapy and high-dose melphalan incorporated within a risk stratification model can help to direct the use of novel treatments.
abstract: Induction chemotherapy followed by high-dose melphalan (HDM) is the standard treatment for fitter patients with myeloma. The place of bortezomib and the thalidomide analogues within this treatment paradigm is yet to be established. We sought to identify patients who may benefit from the introduction of novel agents during their initial management. An intention-to-treat analysis was performed on 383 patients with newly diagnosed myeloma eligible for HDM to determine whether the extent of response to induction therapy and HDM correlated with long-term survival. Early response [complete response (CR) and partial response (PR)] to induction therapy was predictive of overall survival (OS) [median OS, 7.47 years for responders (CR and PR) versus 4.89 years for non-responders; P = 0.035]. The attainment of CR at 3 months post-HDM correlated with a prolonged progression-free survival (PFS) (median PFS, 7.4 years in CR group versus 5.3 years in non-CR group; P = 0.023). This data suggests that, at every stage of treatment, the aim should be to achieve CR. Patients with suboptimal responses could be offered alternative therapy. We propose a multiparametric risk-adapted model that includes response to induction chemotherapy and HDM, for identifying patients who may benefit from novel approaches to treatment.
authors.affiliation: Haemato-oncology Unit, Royal Marsden Hospital, Sutton, Surrey, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Alvares
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Clive
authors.initials: C
authors.lastname: Horton
authors.forename: Gita
authors.initials: G
authors.lastname: Patel
authors.forename: Ray
authors.initials: R
authors.lastname: Powles
authors.forename: Bhawna
authors.initials: B
authors.lastname: Sirohi
authors.forename: Roslin
authors.initials: R
authors.lastname: Zuha
authors.forename: Alex
authors.initials: A
authors.lastname: Gatt
authors.forename: Radovan
authors.initials: R
authors.lastname: Saso
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Treleaven
authors.forename: Claire E
authors.initials: CE
authors.lastname: Dearden
authors.forename: Michael N
authors.initials: MN
authors.lastname: Potter
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ethell
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D012074:Remission Induction; D012306:Risk; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan