Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib

Multicentre, single-arm, phase 2 study

Michael Wang, Leslie L. Popplewell, Robert H. Collins, Jane N. Winter, Andre Goy, Mark S. Kaminski, Nancy L. Bartlett, Patrick Bruce Johnston, John Lister, Suzanne R. Fanning, Joseph M. Tuscano, J. Thaddeus Beck, Hakan Kaya, Anna Robeva, Jenna Fan, Judith Klimovsky, Wing Cheung, Azzeddine Cherfi, Owen A. O'Connor

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)510-518
Number of pages9
JournalBritish Journal of Haematology
Volume165
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Mantle-Cell Lymphoma
Confidence Intervals
Disease-Free Survival
Lymphoma
Safety
Survival
Neutropenia
Antineoplastic Agents
Anemia
Research Personnel
Everolimus
Bortezomib
Population

Keywords

  • Bortezomib
  • Everolimus
  • Mammalian target of rapamycin
  • Mantle cell lymphoma
  • Relapsed/refractory disease

ASJC Scopus subject areas

  • Hematology

Cite this

Wang, M., Popplewell, L. L., Collins, R. H., Winter, J. N., Goy, A., Kaminski, M. S., ... O'Connor, O. A. (2014). Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: Multicentre, single-arm, phase 2 study. British Journal of Haematology, 165(4), 510-518. https://doi.org/10.1111/bjh.12780

Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib : Multicentre, single-arm, phase 2 study. / Wang, Michael; Popplewell, Leslie L.; Collins, Robert H.; Winter, Jane N.; Goy, Andre; Kaminski, Mark S.; Bartlett, Nancy L.; Johnston, Patrick Bruce; 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.

In: British Journal of Haematology, Vol. 165, No. 4, 2014, p. 510-518.

Research output: Contribution to journalArticle

Wang, M, Popplewell, LL, Collins, RH, Winter, JN, Goy, A, Kaminski, MS, Bartlett, NL, Johnston, PB, Lister, J, Fanning, SR, Tuscano, JM, Beck, JT, Kaya, H, Robeva, A, Fan, J, Klimovsky, J, Cheung, W, Cherfi, A & O'Connor, OA 2014, 'Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: Multicentre, single-arm, phase 2 study', British Journal of Haematology, vol. 165, no. 4, pp. 510-518. https://doi.org/10.1111/bjh.12780
Wang, Michael ; Popplewell, Leslie L. ; Collins, Robert H. ; Winter, Jane N. ; Goy, Andre ; Kaminski, Mark S. ; Bartlett, Nancy L. ; Johnston, Patrick Bruce ; 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. / Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib : Multicentre, single-arm, phase 2 study. In: British Journal of Haematology. 2014 ; Vol. 165, No. 4. pp. 510-518.
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