title: Clinical activity of everolimus in relapsed/refractory marginal zone B-cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group.
abstract: The International Extranodal Lymphoma Study Group coordinated a phase II trial to evaluate the activity and safety of everolimus in marginal zone lymphomas (MZLs). Thirty patients with relapsed/refractory MZLs received everolimus for six cycles or until dose-limiting toxicity or progression. Median age was 71 years (range, 51-88 years). Twenty patients had extranodal, six splenic, four nodal MZL. Twenty-four patients had stage III-IV. Median number of prior therapies was two (range 1-5). Seventeen patients had early treatment discontinuation, in most cases due to toxicity. Median number of cycles was 4.5 (range, 1-16). Among the 24 assessable patients, the overall response rate (ORR) was 25% (95% confidence interval: 10-47). Grade 3-4 adverse events were neutropenia and thrombocytopenia (17% of patients, each), infections (17%), mucositis and odontogenic infections (13%) and lung toxicity (3%). The median response duration was 6.8 months (range, 1.4-11.1+). After a median follow-up of 14.5 months, five deaths were reported: four deaths were due to lymphoma, one was due to toxicity. In an intent-to-treat analysis, the projected median progression-free survival was 14 months. The moderate antitumour activity of everolimus in relapsed/refractory MZLs and the observed toxicity limit its therapeutical applicability in these indolent entities. Lower doses of the drug and, perhaps, different strategies including combination with additional agents need to be explored.
authors.affiliation: Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, AOU Maggiore della Carità, Novara, Italy; Haematology Unit, Department of Internal Medicine, Ospedale degli Infermi, Biella, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Conconi
authors.forename: Markus
authors.initials: M
authors.lastname: Raderer
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschetti
authors.forename: Liliana
authors.initials: L
authors.lastname: Devizzi
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Massimo
authors.initials: M
authors.lastname: Magagnoli
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
authors.forename: Barbara
authors.initials: B
authors.lastname: Kiesewetter
authors.forename: Elena
authors.initials: E
authors.lastname: Porro
authors.forename: Anastasios
authors.initials: A
authors.lastname: Stathis
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus
keywords: everolimus; mammalian target of rapamycin; marginal zone B-cell lymphoma; mucosa-associated lymphoid tissue lymphoma; non-Hodgkin lymphoma