title: Bortezomib plus dexamethasone followed by escalating donor lymphocyte infusions for patients with multiple myeloma relapsing or progressing after allogeneic stem cell transplantation.
abstract: Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT) has a poor outcome. To assess the safety and efficacy of bortezomib and dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in myeloma patients relapsing or progressing after alloSCT, a prospective phase II study was designed. The treatment plan consisted of three VD courses followed by escalated doses of DLIs in case of response or at least stable disease. Nineteen patients were enrolled with a median age of 57 years (range, 33 to 67); 14 patients were allografted from human leukocyte antigen-identical siblings and 5 from alternative donors. Sixteen of 19 patients received the planned treatment, but 3 patients did not: 2 patients because of disease progression and 1 refused. After the VD phase the response rate was 62%, with 1 complete remission, 6 very good partial remissions, 5 partial remissions, 2 patients with stable disease, and 5 with progressive disease. After the DLI phase, the response rate was 68%, but a significant upgrade of response was observed: 3 stringent complete remissions, 2 complete remissions, 5 very good partial remissions, 1 partial remission, 4 with stable disease, and 1 with progressive disease. With a median follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival and overall survival rates were 31% and 73%, respectively. Neither unexpected organ toxicities, in particular severe neuropathy, nor severe acute graft-versus-host disease flares were observed. VD-DLIs is a safe treatment for multiple myeloma patients relapsing or progressing after alloSCT and may be effective.
authors.affiliation: Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan, Italy. vittorio.montefusco@istitutotumori.mi.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.forename: Francesco
authors.initials: F
authors.lastname: Spina
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Mauro
authors.initials: M
authors.lastname: Montanari
authors.forename: Alberto
authors.initials: A
authors.lastname: Mussetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sperotto
authors.forename: Ilaria
authors.initials: I
authors.lastname: Scortechini
authors.forename: Anna
authors.initials: A
authors.lastname: Dodero
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011446:Prospective Studies; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D035781:Siblings; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone