Clinical Safety and Efficacy of Nilotinib or Dasatinib in Patients with Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia and Pre-Existing Liver and/or Renal Dysfunction

Koji Sasaki, Amit Lahoti, Elias Jabbour, Preetesh Jain, Sherry Pierce, Gautam Borthakur, Naval Daver, Tapan Kadia, Naveen Pemmaraju, Alessandra Ferrajoli, Susan O'Brien, Hagop Kantarjian, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Background The safety and efficacy of front-line nilotinib and dasatinib in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CML-CP) with pre-existing liver and/or renal dysfunction are unknown. Patients and Methods We analyzed the adverse event rates, response rates, and survival rates of 215 patients with CML-CP with or without renal and/or liver dysfunction who had been treated with front-line nilotinib (n = 108) or dasatinib (n = 107). Results The overall median follow-up period was 49 months. At baseline, 6 dasatinib-treated patients (6%) had mild renal dysfunction and 13 (12%) had mild liver dysfunction. Also, 8 nilotinib-treated patients (7%) had mild renal dysfunction, 1 (1%) moderate renal dysfunction, and 9 (8%) mild liver dysfunction. No significant differences were found in the rate of complete cytogenetic response, major molecular response, or molecular response by a 4.5 log reduction on the international scale between the organ function cohorts. Dasatinib- or nilotinib-treated patients with baseline renal dysfunction had a greater incidence of transient reversible acute kidney injury (P =.011 and P <.001), and nilotinib-treated patients with renal dysfunction had a greater incidence of bleeding (P <.001). Conclusion Patients with CML-CP and mild to moderate renal or liver dysfunction can be safely treated with front-line dasatinib or nilotinib and can achieve response rates similar to those of patients with CML-CP without organ dysfunction.

Original languageEnglish (US)
Pages (from-to)152-162
Number of pages11
JournalClinical Lymphoma, Myeloma and Leukemia
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Kidney
Safety
Liver
Liver Diseases
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Dasatinib
Incidence
Acute Kidney Injury
Cytogenetics
Survival Rate
Hemorrhage

Keywords

  • CML
  • Dasatinib
  • Liver dysfunction
  • Nilotinib
  • Renal dysfunction

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Clinical Safety and Efficacy of Nilotinib or Dasatinib in Patients with Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia and Pre-Existing Liver and/or Renal Dysfunction. / Sasaki, Koji; Lahoti, Amit; Jabbour, Elias; Jain, Preetesh; Pierce, Sherry; Borthakur, Gautam; Daver, Naval; Kadia, Tapan; Pemmaraju, Naveen; Ferrajoli, Alessandra; O'Brien, Susan; Kantarjian, Hagop; Cortes, Jorge.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 16, No. 3, 01.03.2016, p. 152-162.

Research output: Contribution to journalArticle

Sasaki, K, Lahoti, A, Jabbour, E, Jain, P, Pierce, S, Borthakur, G, Daver, N, Kadia, T, Pemmaraju, N, Ferrajoli, A, O'Brien, S, Kantarjian, H & Cortes, J 2016, 'Clinical Safety and Efficacy of Nilotinib or Dasatinib in Patients with Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia and Pre-Existing Liver and/or Renal Dysfunction', Clinical Lymphoma, Myeloma and Leukemia, vol. 16, no. 3, pp. 152-162. https://doi.org/10.1016/j.clml.2015.12.003
Sasaki, Koji ; Lahoti, Amit ; Jabbour, Elias ; Jain, Preetesh ; Pierce, Sherry ; Borthakur, Gautam ; Daver, Naval ; Kadia, Tapan ; Pemmaraju, Naveen ; Ferrajoli, Alessandra ; O'Brien, Susan ; Kantarjian, Hagop ; Cortes, Jorge. / Clinical Safety and Efficacy of Nilotinib or Dasatinib in Patients with Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia and Pre-Existing Liver and/or Renal Dysfunction. In: Clinical Lymphoma, Myeloma and Leukemia. 2016 ; Vol. 16, No. 3. pp. 152-162.
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abstract = "Background The safety and efficacy of front-line nilotinib and dasatinib in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CML-CP) with pre-existing liver and/or renal dysfunction are unknown. Patients and Methods We analyzed the adverse event rates, response rates, and survival rates of 215 patients with CML-CP with or without renal and/or liver dysfunction who had been treated with front-line nilotinib (n = 108) or dasatinib (n = 107). Results The overall median follow-up period was 49 months. At baseline, 6 dasatinib-treated patients (6{\%}) had mild renal dysfunction and 13 (12{\%}) had mild liver dysfunction. Also, 8 nilotinib-treated patients (7{\%}) had mild renal dysfunction, 1 (1{\%}) moderate renal dysfunction, and 9 (8{\%}) mild liver dysfunction. No significant differences were found in the rate of complete cytogenetic response, major molecular response, or molecular response by a 4.5 log reduction on the international scale between the organ function cohorts. Dasatinib- or nilotinib-treated patients with baseline renal dysfunction had a greater incidence of transient reversible acute kidney injury (P =.011 and P <.001), and nilotinib-treated patients with renal dysfunction had a greater incidence of bleeding (P <.001). Conclusion Patients with CML-CP and mild to moderate renal or liver dysfunction can be safely treated with front-line dasatinib or nilotinib and can achieve response rates similar to those of patients with CML-CP without organ dysfunction.",
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AU - Sasaki, Koji

AU - Lahoti, Amit

AU - Jabbour, Elias

AU - Jain, Preetesh

AU - Pierce, Sherry

AU - Borthakur, Gautam

AU - Daver, Naval

AU - Kadia, Tapan

AU - Pemmaraju, Naveen

AU - Ferrajoli, Alessandra

AU - O'Brien, Susan

AU - Kantarjian, Hagop

AU - Cortes, Jorge

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background The safety and efficacy of front-line nilotinib and dasatinib in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CML-CP) with pre-existing liver and/or renal dysfunction are unknown. Patients and Methods We analyzed the adverse event rates, response rates, and survival rates of 215 patients with CML-CP with or without renal and/or liver dysfunction who had been treated with front-line nilotinib (n = 108) or dasatinib (n = 107). Results The overall median follow-up period was 49 months. At baseline, 6 dasatinib-treated patients (6%) had mild renal dysfunction and 13 (12%) had mild liver dysfunction. Also, 8 nilotinib-treated patients (7%) had mild renal dysfunction, 1 (1%) moderate renal dysfunction, and 9 (8%) mild liver dysfunction. No significant differences were found in the rate of complete cytogenetic response, major molecular response, or molecular response by a 4.5 log reduction on the international scale between the organ function cohorts. Dasatinib- or nilotinib-treated patients with baseline renal dysfunction had a greater incidence of transient reversible acute kidney injury (P =.011 and P <.001), and nilotinib-treated patients with renal dysfunction had a greater incidence of bleeding (P <.001). Conclusion Patients with CML-CP and mild to moderate renal or liver dysfunction can be safely treated with front-line dasatinib or nilotinib and can achieve response rates similar to those of patients with CML-CP without organ dysfunction.

AB - Background The safety and efficacy of front-line nilotinib and dasatinib in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CML-CP) with pre-existing liver and/or renal dysfunction are unknown. Patients and Methods We analyzed the adverse event rates, response rates, and survival rates of 215 patients with CML-CP with or without renal and/or liver dysfunction who had been treated with front-line nilotinib (n = 108) or dasatinib (n = 107). Results The overall median follow-up period was 49 months. At baseline, 6 dasatinib-treated patients (6%) had mild renal dysfunction and 13 (12%) had mild liver dysfunction. Also, 8 nilotinib-treated patients (7%) had mild renal dysfunction, 1 (1%) moderate renal dysfunction, and 9 (8%) mild liver dysfunction. No significant differences were found in the rate of complete cytogenetic response, major molecular response, or molecular response by a 4.5 log reduction on the international scale between the organ function cohorts. Dasatinib- or nilotinib-treated patients with baseline renal dysfunction had a greater incidence of transient reversible acute kidney injury (P =.011 and P <.001), and nilotinib-treated patients with renal dysfunction had a greater incidence of bleeding (P <.001). Conclusion Patients with CML-CP and mild to moderate renal or liver dysfunction can be safely treated with front-line dasatinib or nilotinib and can achieve response rates similar to those of patients with CML-CP without organ dysfunction.

KW - CML

KW - Dasatinib

KW - Liver dysfunction

KW - Nilotinib

KW - Renal dysfunction

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