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

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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    Niesvizky, R., Badros, A. Z., Costa, L. J., Ely, S. A., Singhal, S. B., Stadtmauer, E. A., Haideri, N. A., Yacoub, A., Hess, G., Lentzsch, S., Spicka, I., Chanan-Khan, A. A., Raab, M. S., Tarantolo, S., Vij, R., Zonder, J. A., Huang, X., Jayabalan, D., Di Liberto, M., ... Chen-Kiang, S. (2015). Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Leukemia and Lymphoma, 56(12), 3320-3328. https://doi.org/10.3109/10428194.2015.1030641