Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma

Mayo Phase Consortium

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Dysregulation of cyclin-dependent kinases is a hallmark of myeloma, and specifically, cdk5 inhibition can enhance the activity of proteasome inhibitors in vitro. Dinaciclib is a novel potent small molecule inhibitor of cyclin-dependent kinases (CDK)1, CDK2, CDK5, and CDK9. Patients with relapsed multiple myeloma and ≤5 prior lines of therapy, with measurable disease, were enrolled. Dinaciclib was administered on day 1 of a 21-day cycle at doses of 30 to 50 mg/m2. Overall, 27 evaluable patients were accrued; the median number of prior therapies was 4. The dose level of 50 mg/m2 was determined to be the maximally tolerated dose. The overall confirmed partial response rate (PR) was 3 of 27 (11%), including 1 patient at the 30 mg/m2 dose (1 very good PR [VGPR]) and 2 patients at the 40 mg/m2 dose (1 VGPR and 1 PR). In addition, 2 patients at the 50mg/mg2 dose achieved a minimal response (clinical benefit rate, 19%). Leukopenia, thrombocytopenia, gastrointestinal symptoms, alopecia, and fatigue were the most common adverse events. The current study demonstrates single agent activity of dinaciclib in relapsed myeloma, with 2 patients achieving a deep response (VGPR) and 10 patients obtaining some degree of M protein stabilization or decrease.

Original languageEnglish (US)
Pages (from-to)443-448
Number of pages6
JournalBlood
Volume125
Issue number3
DOIs
StatePublished - Jan 15 2015

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Cyclin-Dependent Kinases
Multiple Myeloma
CDC2 Protein Kinase
Proteasome Inhibitors
Stabilization
Fatigue of materials
Molecules
Maximum Tolerated Dose
Alopecia
Leukopenia
dinaciclib
Thrombocytopenia
Proteins
Fatigue
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. / Mayo Phase Consortium.

In: Blood, Vol. 125, No. 3, 15.01.2015, p. 443-448.

Research output: Contribution to journalArticle

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abstract = "Dysregulation of cyclin-dependent kinases is a hallmark of myeloma, and specifically, cdk5 inhibition can enhance the activity of proteasome inhibitors in vitro. Dinaciclib is a novel potent small molecule inhibitor of cyclin-dependent kinases (CDK)1, CDK2, CDK5, and CDK9. Patients with relapsed multiple myeloma and ≤5 prior lines of therapy, with measurable disease, were enrolled. Dinaciclib was administered on day 1 of a 21-day cycle at doses of 30 to 50 mg/m2. Overall, 27 evaluable patients were accrued; the median number of prior therapies was 4. The dose level of 50 mg/m2 was determined to be the maximally tolerated dose. The overall confirmed partial response rate (PR) was 3 of 27 (11{\%}), including 1 patient at the 30 mg/m2 dose (1 very good PR [VGPR]) and 2 patients at the 40 mg/m2 dose (1 VGPR and 1 PR). In addition, 2 patients at the 50mg/mg2 dose achieved a minimal response (clinical benefit rate, 19{\%}). Leukopenia, thrombocytopenia, gastrointestinal symptoms, alopecia, and fatigue were the most common adverse events. The current study demonstrates single agent activity of dinaciclib in relapsed myeloma, with 2 patients achieving a deep response (VGPR) and 10 patients obtaining some degree of M protein stabilization or decrease.",
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AU - Zonder, Jeffrey

AU - Callander, Natalie

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