Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma

Ruben Niesvizky*, Ashraf Z. Badros, Luciano J. Costa, Scott A. Ely, Seema B. Singhal, Edward A. Stadtmauer, Nisreen A. Haideri, Abdulraheem Yacoub, Georg Hess, Suzanne Lentzsch, Ivan Spicka, Asher A. Chanan-Khan, Marc S. Raab, Stefano Tarantolo, Ravi Vij, Jeffrey A. Zonder, Xiangao Huang, David Jayabalan, Maurizio Di Liberto, Xin HuangYuqiu Jiang, Sindy T. Kim, Sophia Randolph, Selina Chen-Kiang

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade ≤ 3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients.

Original languageEnglish (US)
Pages (from-to)3320-3328
Number of pages9
JournalLeukemia and Lymphoma
Volume56
Issue number12
DOIs
StatePublished - Dec 2 2015

Keywords

  • CDK 4/6
  • Cell cycle
  • cyclin-dependent kinase 4/6
  • multiple myeloma
  • palbociclib

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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