title: Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: multicentre, single-arm, phase 2 study.
abstract: The multicentre, open-label, two-stage, single-arm, phase 2, PILLAR (PIvotaL Lymphoma triAls of RAD001)-1 study (NCT00702052) assessed the efficacy and safety of everolimus 10 mg/d in adults with confirmed mantle cell lymphoma (MCL) refractory to or intolerant of bortezomib who received ≥1 other antineoplastic agent, either separately or in combination with bortezomib. Primary endpoint was overall response rate (ORR) per investigator review according to the response criteria for malignant lymphoma. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Fifty-eight patients were enrolled from August 2008-January 2011. Five partial responses were observed (ORR 8·6%; 90% confidence interval [CI] 3·5-17·3%); the study did not meet the prespecified objective of ≥8 objective responses among 57 patients. Median PFS and OS were 4·4 months (95% CI 3·5-6·1) and 16·9 months (95% CI 14·4-29·9), respectively. Grade 3/4 non-haematological toxicities occurred in 70·7% of patients. Based on laboratory values, grade 3/4 thrombocytopenia, neutropenia and anaemia occurred in 13·8%, 13·8% and 8·6% of patients, respectively. Everolimus demonstrated modest activity and acceptable tolerability in heavily pretreated patients with MCL refractory to or intolerant of bortezomib. Future studies evaluating everolimus in a less refractory population or in combination with other targeted therapies in refractory MCL are warranted.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Popplewell
authors.forename: Robert H
authors.initials: RH
authors.lastname: Collins
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Johnston
authors.forename: John
authors.initials: J
authors.lastname: Lister
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Fanning
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Tuscano
authors.forename: J Thaddeus
authors.initials: JT
authors.lastname: Beck
authors.forename: Hakan
authors.initials: H
authors.lastname: Kaya
authors.forename: Anna
authors.initials: A
authors.lastname: Robeva
authors.forename: Jenna
authors.initials: J
authors.lastname: Fan
authors.forename: Judith
authors.initials: J
authors.lastname: Klimovsky
authors.forename: Wing
authors.initials: W
authors.lastname: Cheung
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Cherfi
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D011014:Pneumonia / Q000139:chemically induced; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016879:Salvage Therapy; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D000068338:Everolimus; D020123:Sirolimus
keywords: bortezomib; everolimus; mammalian target of rapamycin; mantle cell lymphoma; relapsed/refractory disease