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Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: multicentre, single‐arm, phase 2 study
Author(s) -
Wang Michael,
Popplewell Leslie L.,
Collins Robert H.,
Winter Jane N.,
Goy Andre,
Kaminski Mark S.,
Bartlett Nancy L.,
Johnston Patrick B.,
Lister John,
Fanning Suzanne R.,
Tuscano Joseph M.,
Beck J. Thaddeus,
Kaya Hakan,
Robeva Anna,
Fan Jenna,
Klimovsky Judith,
Cheung Wing,
Cherfi Azzeddine,
O'Connor Owen A.
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12780
Subject(s) - medicine , mantle cell lymphoma , everolimus , bortezomib , tolerability , neutropenia , clinical endpoint , refractory (planetary science) , phases of clinical research , febrile neutropenia , population , gastroenterology , progression free survival , oncology , temsirolimus , surgery , adverse effect , lymphoma , clinical trial , chemotherapy , multiple myeloma , apoptosis , biochemistry , chemistry , physics , protein kinase b , environmental health , discovery and development of mtor inhibitors , astrobiology
Summary The multicentre, open‐label, two‐stage, single‐arm, phase 2, PILLAR ( P IvotaL L ymphoma triAls of RAD 001)‐1 study ( NCT 00702052) 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.