Life after ponatinib failure: outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting

Prajwal Boddu, Abdul Rashid Shah, Gautam Borthakur, Srdan Verstovsek, Guillermo Garcia-Manero, Naval Daver, Tapan Kadia, Farhad Ravandi, Nitin Jain, Ahmad Alhuraiji, Jan Burger, Steven Kornblau, Sherry Pierce, Sara Dellasala, Elias Jabbour, Hagop Kantarjian, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1). At discontinuation, 14 were still in CP, three had progressed to AP and two to blast phase (BP). Three CP patients improved their cytogenetic response (CyR) to complete CyR (CCyR), two after SCT and one on omacetaxine. None of the 12 patients, without a major cytogenetic response at ponatinib discontinuation, including all patients treated with subsequent TKIs, responded to therapy. Seventeen AP patients, stopped ponatinib due to resistance (n = 15) or intolerance (n = 2). At discontinuation, 14 were still in AP and three had progressed to BP. Four patients were treated with SCT and one achieved major molecular response. None of the 12 patients treated with non-SCT approaches responded to subsequent therapy. Median survival for all patients was 16.6 months after ponatinib discontinuation (31, 9 and 13 months for patients in CP, AP and BP, respectively). Median survival was 60 months for patients who discontinued ponatinib for toxicity and 11 months for those who discontinued for resistance. Long-term outcome of patients with ponatinib failure are poor with estimated one-year OS and EFS rates of 54% and 40%, respectively. New treatment options are required for this subset of patients.

Original languageEnglish (US)
Pages (from-to)1312-1322
Number of pages11
JournalLeukemia and Lymphoma
Volume59
Issue number6
DOIs
StatePublished - Jun 3 2018

Fingerprint

Blast Crisis
ponatinib
Cytogenetics
Protein-Tyrosine Kinases
Survival
Stem Cell Transplantation
Therapeutics

Keywords

  • Ponatinib
  • accelerated phase
  • chronic myelogenous leukemia
  • chronic phase
  • outcomes
  • salvage

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Life after ponatinib failure : outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting. / Boddu, Prajwal; Shah, Abdul Rashid; Borthakur, Gautam; Verstovsek, Srdan; Garcia-Manero, Guillermo; Daver, Naval; Kadia, Tapan; Ravandi, Farhad; Jain, Nitin; Alhuraiji, Ahmad; Burger, Jan; Kornblau, Steven; Pierce, Sherry; Dellasala, Sara; Jabbour, Elias; Kantarjian, Hagop; Cortes, Jorge.

In: Leukemia and Lymphoma, Vol. 59, No. 6, 03.06.2018, p. 1312-1322.

Research output: Contribution to journalArticle

Boddu, P, Shah, AR, Borthakur, G, Verstovsek, S, Garcia-Manero, G, Daver, N, Kadia, T, Ravandi, F, Jain, N, Alhuraiji, A, Burger, J, Kornblau, S, Pierce, S, Dellasala, S, Jabbour, E, Kantarjian, H & Cortes, J 2018, 'Life after ponatinib failure: outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting', Leukemia and Lymphoma, vol. 59, no. 6, pp. 1312-1322. https://doi.org/10.1080/10428194.2017.1379076
Boddu, Prajwal ; Shah, Abdul Rashid ; Borthakur, Gautam ; Verstovsek, Srdan ; Garcia-Manero, Guillermo ; Daver, Naval ; Kadia, Tapan ; Ravandi, Farhad ; Jain, Nitin ; Alhuraiji, Ahmad ; Burger, Jan ; Kornblau, Steven ; Pierce, Sherry ; Dellasala, Sara ; Jabbour, Elias ; Kantarjian, Hagop ; Cortes, Jorge. / Life after ponatinib failure : outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting. In: Leukemia and Lymphoma. 2018 ; Vol. 59, No. 6. pp. 1312-1322.
@article{af911de00b43445686ad5521ceaf97a9,
title = "Life after ponatinib failure: outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting",
abstract = "Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1). At discontinuation, 14 were still in CP, three had progressed to AP and two to blast phase (BP). Three CP patients improved their cytogenetic response (CyR) to complete CyR (CCyR), two after SCT and one on omacetaxine. None of the 12 patients, without a major cytogenetic response at ponatinib discontinuation, including all patients treated with subsequent TKIs, responded to therapy. Seventeen AP patients, stopped ponatinib due to resistance (n = 15) or intolerance (n = 2). At discontinuation, 14 were still in AP and three had progressed to BP. Four patients were treated with SCT and one achieved major molecular response. None of the 12 patients treated with non-SCT approaches responded to subsequent therapy. Median survival for all patients was 16.6 months after ponatinib discontinuation (31, 9 and 13 months for patients in CP, AP and BP, respectively). Median survival was 60 months for patients who discontinued ponatinib for toxicity and 11 months for those who discontinued for resistance. Long-term outcome of patients with ponatinib failure are poor with estimated one-year OS and EFS rates of 54{\%} and 40{\%}, respectively. New treatment options are required for this subset of patients.",
keywords = "Ponatinib, accelerated phase, chronic myelogenous leukemia, chronic phase, outcomes, salvage",
author = "Prajwal Boddu and Shah, {Abdul Rashid} and Gautam Borthakur and Srdan Verstovsek and Guillermo Garcia-Manero and Naval Daver and Tapan Kadia and Farhad Ravandi and Nitin Jain and Ahmad Alhuraiji and Jan Burger and Steven Kornblau and Sherry Pierce and Sara Dellasala and Elias Jabbour and Hagop Kantarjian and Jorge Cortes",
year = "2018",
month = "6",
day = "3",
doi = "10.1080/10428194.2017.1379076",
language = "English (US)",
volume = "59",
pages = "1312--1322",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",
number = "6",

}

TY - JOUR

T1 - Life after ponatinib failure

T2 - outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting

AU - Boddu, Prajwal

AU - Shah, Abdul Rashid

AU - Borthakur, Gautam

AU - Verstovsek, Srdan

AU - Garcia-Manero, Guillermo

AU - Daver, Naval

AU - Kadia, Tapan

AU - Ravandi, Farhad

AU - Jain, Nitin

AU - Alhuraiji, Ahmad

AU - Burger, Jan

AU - Kornblau, Steven

AU - Pierce, Sherry

AU - Dellasala, Sara

AU - Jabbour, Elias

AU - Kantarjian, Hagop

AU - Cortes, Jorge

PY - 2018/6/3

Y1 - 2018/6/3

N2 - Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1). At discontinuation, 14 were still in CP, three had progressed to AP and two to blast phase (BP). Three CP patients improved their cytogenetic response (CyR) to complete CyR (CCyR), two after SCT and one on omacetaxine. None of the 12 patients, without a major cytogenetic response at ponatinib discontinuation, including all patients treated with subsequent TKIs, responded to therapy. Seventeen AP patients, stopped ponatinib due to resistance (n = 15) or intolerance (n = 2). At discontinuation, 14 were still in AP and three had progressed to BP. Four patients were treated with SCT and one achieved major molecular response. None of the 12 patients treated with non-SCT approaches responded to subsequent therapy. Median survival for all patients was 16.6 months after ponatinib discontinuation (31, 9 and 13 months for patients in CP, AP and BP, respectively). Median survival was 60 months for patients who discontinued ponatinib for toxicity and 11 months for those who discontinued for resistance. Long-term outcome of patients with ponatinib failure are poor with estimated one-year OS and EFS rates of 54% and 40%, respectively. New treatment options are required for this subset of patients.

AB - Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1). At discontinuation, 14 were still in CP, three had progressed to AP and two to blast phase (BP). Three CP patients improved their cytogenetic response (CyR) to complete CyR (CCyR), two after SCT and one on omacetaxine. None of the 12 patients, without a major cytogenetic response at ponatinib discontinuation, including all patients treated with subsequent TKIs, responded to therapy. Seventeen AP patients, stopped ponatinib due to resistance (n = 15) or intolerance (n = 2). At discontinuation, 14 were still in AP and three had progressed to BP. Four patients were treated with SCT and one achieved major molecular response. None of the 12 patients treated with non-SCT approaches responded to subsequent therapy. Median survival for all patients was 16.6 months after ponatinib discontinuation (31, 9 and 13 months for patients in CP, AP and BP, respectively). Median survival was 60 months for patients who discontinued ponatinib for toxicity and 11 months for those who discontinued for resistance. Long-term outcome of patients with ponatinib failure are poor with estimated one-year OS and EFS rates of 54% and 40%, respectively. New treatment options are required for this subset of patients.

KW - Ponatinib

KW - accelerated phase

KW - chronic myelogenous leukemia

KW - chronic phase

KW - outcomes

KW - salvage

UR - http://www.scopus.com/inward/record.url?scp=85030533973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030533973&partnerID=8YFLogxK

U2 - 10.1080/10428194.2017.1379076

DO - 10.1080/10428194.2017.1379076

M3 - Article

C2 - 28972430

AN - SCOPUS:85030533973

VL - 59

SP - 1312

EP - 1322

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

IS - 6

ER -