Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: Final results from the PILLAR-2 randomized phase III trial

T. E. Witzig, K. Tobinai, L. Rigacci, T. Ikeda, A. Vanazzi, M. Hino, Y. Shi, J. Mayer, L. J. Costa, C. D. Bermudez Silva, J. Zhu, D. Belada, K. Bouabdallah, J. G. Kattan, J. Kuruvilla, W. S. Kim, J. F. Larouche, M. Ogura, M. Ozcan, L. FayadC. Wu, J. Fan, A. L. Louveau, M. Voi, F. Cavalli

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI)≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has singleagent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI≥3) DLBCL and a positron emission tomography/computed tomographyconfirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n=372) or placebo (n=370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P=0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036

Original languageEnglish (US)
Pages (from-to)707-714
Number of pages8
JournalAnnals of Oncology
Volume29
Issue number3
DOIs
StatePublished - Mar 1 2018

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Keywords

  • Adjuvant therapy
  • Everolimus
  • Large cell lymphoma

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Witzig, T. E., Tobinai, K., Rigacci, L., Ikeda, T., Vanazzi, A., Hino, M., Shi, Y., Mayer, J., Costa, L. J., Bermudez Silva, C. D., Zhu, J., Belada, D., Bouabdallah, K., Kattan, J. G., Kuruvilla, J., Kim, W. S., Larouche, J. F., Ogura, M., Ozcan, M., ... Cavalli, F. (2018). Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: Final results from the PILLAR-2 randomized phase III trial. Annals of Oncology, 29(3), 707-714. https://doi.org/10.1093/annonc/mdx764