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 Huang; Yuqiu Jiang; Sindy T. Kim; Sophia Randolph; Selina Chen-Kiang

doi:10.3109/10428194.2015.1030641

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

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	3320-3328
Number of pages	9
Journal	Leukemia and Lymphoma
Volume	56
Issue number	12
DOIs	https://doi.org/10.3109/10428194.2015.1030641
State	Published - Dec 2 2015

Funding

This study was sponsored by Pfizer Inc. The authors would like to thank Colin P. Mitchell, PhD, and Tiffany Brake, PhD, from Complete Healthcare Communications, Inc., who provided medical writing assistance, which was funded by Pfizer Inc.

Keywords

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

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3109/10428194.2015.1030641

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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

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

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.",

keywords = "CDK 4/6, Cell cycle, cyclin-dependent kinase 4/6, multiple myeloma, palbociclib",

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

note = "Publisher Copyright: {\textcopyright} 2015 Informa UK, Ltd.",

year = "2015",

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doi = "10.3109/10428194.2015.1030641",

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Niesvizky, R, Badros, AZ, Costa, LJ, Ely, SA, Singhal, SB, Stadtmauer, EA, Haideri, NA, Yacoub, A, Hess, G, Lentzsch, S, Spicka, I, Chanan-Khan, AA, Raab, MS, Tarantolo, S, Vij, R, Zonder, JA, Huang, X, Jayabalan, D, Di Liberto, M, Huang, X, Jiang, Y, Kim, ST, Randolph, S & 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, vol. 56, no. 12, pp. 3320-3328. https://doi.org/10.3109/10428194.2015.1030641

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AU - Niesvizky, Ruben

AU - Badros, Ashraf Z.

AU - Costa, Luciano J.

AU - Ely, Scott A.

AU - Singhal, Seema B.

AU - Stadtmauer, Edward A.

AU - Haideri, Nisreen A.

AU - Yacoub, Abdulraheem

AU - Hess, Georg

AU - Lentzsch, Suzanne

AU - Spicka, Ivan

AU - Chanan-Khan, Asher A.

AU - Raab, Marc S.

AU - Tarantolo, Stefano

AU - Vij, Ravi

AU - Zonder, Jeffrey A.

AU - Huang, Xiangao

AU - Jayabalan, David

AU - Di Liberto, Maurizio

AU - Huang, Xin

AU - Jiang, Yuqiu

AU - Kim, Sindy T.

AU - Randolph, Sophia

AU - Chen-Kiang, Selina

PY - 2015/12/2

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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