Clinical Experience With Ibrutinib Alone or in Combination With Either Cytarabine or Azacitidine in Patients With Acute Myeloid Leukemia

Jorge E. Cortes, Brian A. Jonas, Thorsten Graef, Ying Luan, Anthony S. Stein

Research output: Contribution to journalArticle

Abstract

Background: Preclinical studies have suggested a role for Bruton tyrosine kinase (BTK) as a potential therapeutic target in acute myeloid leukemia (AML), and anti-AML activity in vivo has been demonstrated with BTK inhibitors. Patients and Methods: In this open-label phase 2a study, patients with AML were treated with ibrutinib 560 mg per day alone (cohort 1; n = 7), or ibrutinib in combination with either cytarabine 20 mg administered subcutaneously twice daily for 10 days of a 28-day cycle (cohort 2; n = 21) or azacitidine 75 mg/m2 administered intravenously once daily on days 1 to 7 of a 28-day cycle (cohort 3; n = 8). Best overall response (primary end point), overall survival, and safety were summarized. Results: A total of 36 patients were enrolled and received treatment; median duration of ibrutinib treatment was 5.4 weeks, and median time on study was 16 months. Of 24 patients evaluable for response, 1 partial remission (cohort 3) and 1 complete remission (cohort 2) were observed; the remaining responses were treatment failures. Median overall survival was 4.0 months in cohort 1, 2.2 months in cohort 2, 2.8 months in cohort 3, and 2.4 months for the overall population. No unexpected safety signals were identified. Grade 3 or higher adverse events that occurred in ≥ 10% of patients included AML progression, febrile neutropenia, pneumonia, anemia, thrombocytopenia, fatigue, asthenia, and respiratory failure. Conclusion: Ibrutinib alone or in combination with cytarabine or azacitidine demonstrated an acceptable safety profile. However, limited efficacy with ibrutinib was observed in patients with AML. Preclinical studies have suggested that ibrutinib may have a clinical benefit in acute myeloid leukemia (AML). Treatment with ibrutinib alone or in combination with cytarabine or azacitidine was evaluated in 36 patients with AML. The study was terminated because of limited efficacy. Safety was consistent with established safety profiles of the individual drugs. The potential utility of ibrutinib in AML remains uncertain.

Original languageEnglish (US)
Pages (from-to)509-515.e1
JournalClinical Lymphoma, Myeloma and Leukemia
Volume19
Issue number8
DOIs
StatePublished - Aug 2019
Externally publishedYes

Fingerprint

Azacitidine
Cytarabine
Acute Myeloid Leukemia
Safety
Asthenia
Febrile Neutropenia
Survival
PCI 32765
Therapeutics
Treatment Failure
Respiratory Insufficiency
Thrombocytopenia
Fatigue
Anemia
Pneumonia

Keywords

  • BTK inhibitor
  • Chemotherapy
  • Efficacy
  • Hypomethylating agent
  • Safety

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Clinical Experience With Ibrutinib Alone or in Combination With Either Cytarabine or Azacitidine in Patients With Acute Myeloid Leukemia. / Cortes, Jorge E.; Jonas, Brian A.; Graef, Thorsten; Luan, Ying; Stein, Anthony S.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 19, No. 8, 08.2019, p. 509-515.e1.

Research output: Contribution to journalArticle

@article{48c33c38efd046049362bda6dc2a0b8e,
title = "Clinical Experience With Ibrutinib Alone or in Combination With Either Cytarabine or Azacitidine in Patients With Acute Myeloid Leukemia",
abstract = "Background: Preclinical studies have suggested a role for Bruton tyrosine kinase (BTK) as a potential therapeutic target in acute myeloid leukemia (AML), and anti-AML activity in vivo has been demonstrated with BTK inhibitors. Patients and Methods: In this open-label phase 2a study, patients with AML were treated with ibrutinib 560 mg per day alone (cohort 1; n = 7), or ibrutinib in combination with either cytarabine 20 mg administered subcutaneously twice daily for 10 days of a 28-day cycle (cohort 2; n = 21) or azacitidine 75 mg/m2 administered intravenously once daily on days 1 to 7 of a 28-day cycle (cohort 3; n = 8). Best overall response (primary end point), overall survival, and safety were summarized. Results: A total of 36 patients were enrolled and received treatment; median duration of ibrutinib treatment was 5.4 weeks, and median time on study was 16 months. Of 24 patients evaluable for response, 1 partial remission (cohort 3) and 1 complete remission (cohort 2) were observed; the remaining responses were treatment failures. Median overall survival was 4.0 months in cohort 1, 2.2 months in cohort 2, 2.8 months in cohort 3, and 2.4 months for the overall population. No unexpected safety signals were identified. Grade 3 or higher adverse events that occurred in ≥ 10{\%} of patients included AML progression, febrile neutropenia, pneumonia, anemia, thrombocytopenia, fatigue, asthenia, and respiratory failure. Conclusion: Ibrutinib alone or in combination with cytarabine or azacitidine demonstrated an acceptable safety profile. However, limited efficacy with ibrutinib was observed in patients with AML. Preclinical studies have suggested that ibrutinib may have a clinical benefit in acute myeloid leukemia (AML). Treatment with ibrutinib alone or in combination with cytarabine or azacitidine was evaluated in 36 patients with AML. The study was terminated because of limited efficacy. Safety was consistent with established safety profiles of the individual drugs. The potential utility of ibrutinib in AML remains uncertain.",
keywords = "BTK inhibitor, Chemotherapy, Efficacy, Hypomethylating agent, Safety",
author = "Cortes, {Jorge E.} and Jonas, {Brian A.} and Thorsten Graef and Ying Luan and Stein, {Anthony S.}",
year = "2019",
month = "8",
doi = "10.1016/j.clml.2019.05.008",
language = "English (US)",
volume = "19",
pages = "509--515.e1",
journal = "Clinical Lymphoma, Myeloma and Leukemia",
issn = "2152-2650",
publisher = "Cancer Media Group",
number = "8",

}

TY - JOUR

T1 - Clinical Experience With Ibrutinib Alone or in Combination With Either Cytarabine or Azacitidine in Patients With Acute Myeloid Leukemia

AU - Cortes, Jorge E.

AU - Jonas, Brian A.

AU - Graef, Thorsten

AU - Luan, Ying

AU - Stein, Anthony S.

PY - 2019/8

Y1 - 2019/8

N2 - Background: Preclinical studies have suggested a role for Bruton tyrosine kinase (BTK) as a potential therapeutic target in acute myeloid leukemia (AML), and anti-AML activity in vivo has been demonstrated with BTK inhibitors. Patients and Methods: In this open-label phase 2a study, patients with AML were treated with ibrutinib 560 mg per day alone (cohort 1; n = 7), or ibrutinib in combination with either cytarabine 20 mg administered subcutaneously twice daily for 10 days of a 28-day cycle (cohort 2; n = 21) or azacitidine 75 mg/m2 administered intravenously once daily on days 1 to 7 of a 28-day cycle (cohort 3; n = 8). Best overall response (primary end point), overall survival, and safety were summarized. Results: A total of 36 patients were enrolled and received treatment; median duration of ibrutinib treatment was 5.4 weeks, and median time on study was 16 months. Of 24 patients evaluable for response, 1 partial remission (cohort 3) and 1 complete remission (cohort 2) were observed; the remaining responses were treatment failures. Median overall survival was 4.0 months in cohort 1, 2.2 months in cohort 2, 2.8 months in cohort 3, and 2.4 months for the overall population. No unexpected safety signals were identified. Grade 3 or higher adverse events that occurred in ≥ 10% of patients included AML progression, febrile neutropenia, pneumonia, anemia, thrombocytopenia, fatigue, asthenia, and respiratory failure. Conclusion: Ibrutinib alone or in combination with cytarabine or azacitidine demonstrated an acceptable safety profile. However, limited efficacy with ibrutinib was observed in patients with AML. Preclinical studies have suggested that ibrutinib may have a clinical benefit in acute myeloid leukemia (AML). Treatment with ibrutinib alone or in combination with cytarabine or azacitidine was evaluated in 36 patients with AML. The study was terminated because of limited efficacy. Safety was consistent with established safety profiles of the individual drugs. The potential utility of ibrutinib in AML remains uncertain.

AB - Background: Preclinical studies have suggested a role for Bruton tyrosine kinase (BTK) as a potential therapeutic target in acute myeloid leukemia (AML), and anti-AML activity in vivo has been demonstrated with BTK inhibitors. Patients and Methods: In this open-label phase 2a study, patients with AML were treated with ibrutinib 560 mg per day alone (cohort 1; n = 7), or ibrutinib in combination with either cytarabine 20 mg administered subcutaneously twice daily for 10 days of a 28-day cycle (cohort 2; n = 21) or azacitidine 75 mg/m2 administered intravenously once daily on days 1 to 7 of a 28-day cycle (cohort 3; n = 8). Best overall response (primary end point), overall survival, and safety were summarized. Results: A total of 36 patients were enrolled and received treatment; median duration of ibrutinib treatment was 5.4 weeks, and median time on study was 16 months. Of 24 patients evaluable for response, 1 partial remission (cohort 3) and 1 complete remission (cohort 2) were observed; the remaining responses were treatment failures. Median overall survival was 4.0 months in cohort 1, 2.2 months in cohort 2, 2.8 months in cohort 3, and 2.4 months for the overall population. No unexpected safety signals were identified. Grade 3 or higher adverse events that occurred in ≥ 10% of patients included AML progression, febrile neutropenia, pneumonia, anemia, thrombocytopenia, fatigue, asthenia, and respiratory failure. Conclusion: Ibrutinib alone or in combination with cytarabine or azacitidine demonstrated an acceptable safety profile. However, limited efficacy with ibrutinib was observed in patients with AML. Preclinical studies have suggested that ibrutinib may have a clinical benefit in acute myeloid leukemia (AML). Treatment with ibrutinib alone or in combination with cytarabine or azacitidine was evaluated in 36 patients with AML. The study was terminated because of limited efficacy. Safety was consistent with established safety profiles of the individual drugs. The potential utility of ibrutinib in AML remains uncertain.

KW - BTK inhibitor

KW - Chemotherapy

KW - Efficacy

KW - Hypomethylating agent

KW - Safety

UR - http://www.scopus.com/inward/record.url?scp=85067295024&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067295024&partnerID=8YFLogxK

U2 - 10.1016/j.clml.2019.05.008

DO - 10.1016/j.clml.2019.05.008

M3 - Article

C2 - 31227358

AN - SCOPUS:85067295024

VL - 19

SP - 509-515.e1

JO - Clinical Lymphoma, Myeloma and Leukemia

JF - Clinical Lymphoma, Myeloma and Leukemia

SN - 2152-2650

IS - 8

ER -