Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Issue 12 (2nd December 2015)

• Record Type: Journal Article
• Authors: Niesvizky, Ruben; Badros, Ashraf Z.; Costa, Luciano J.; Ely, Scott A.; Singhal, Seema B.; Stadtmauer, Edward A.; Haideri, Nisreen A.; Yacoub, Abdulraheem; Hess, Georg; Lentzsch, Suzanne; Spicka, Ivan; Chanan-Khan, Asher A.; Raab, Marc S.; Tarantolo, Stefano; Vij, Ravi; Zonder, Jeffrey A.; Huang, Xiangao; Jayabalan, David; Di Liberto, Maurizio; Huang, Xin; Jiang, Yuqiu; Kim, Sindy T.; Randolph, Sophia; Chen-Kiang, Selina
• Is Part Of: Leukemia & lymphoma. Volume 56:Issue 12(2015:Dec.)
• Page Start: 3320
• Page End: 3328
• Publication Date: 2015-12-02
• Subjects: Cell cycle -- CDK 4/6 -- cyclin-dependent kinase 4/6 -- multiple myeloma -- palbociclib; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2015.1030641
• Languages: English
• ISSNs: 1042-8194

Abstract

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/m 2 (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.