Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib

Susan Branford, Dong Wook Kim, Simona Soverini, Ariful Haque, Yaping Shou, Richard C. Woodman, Hagop M. Kantarjian, Giovanni Martinelli, Jerald P. Radich, Giuseppe Saglio, Andreas Hochhaus, Timothy P. Hughes, Martin C. Müller

Research output: Contribution to journalArticle

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Abstract

Purpose: The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients and Methods: Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). Results: BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR-ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%. Conclusion: Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.

LanguageEnglish
Pages4323-4329
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number35
DOIs
Publication statusPublished - 10 Dec 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Branford, Susan ; Kim, Dong Wook ; Soverini, Simona ; Haque, Ariful ; Shou, Yaping ; Woodman, Richard C. ; Kantarjian, Hagop M. ; Martinelli, Giovanni ; Radich, Jerald P. ; Saglio, Giuseppe ; Hochhaus, Andreas ; Hughes, Timothy P. ; Müller, Martin C. / Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 35. pp. 4323-4329.
@article{8ca6f5c1e3414289b7d0497daea8b8f2,
title = "Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib",
abstract = "Purpose: The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients and Methods: Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). Results: BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1{\%} to ≤ 10{\%} at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10{\%} (53{\%} v 16{\%}). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1{\%} to ≤ 1{\%}, > 1{\%} to ≤ 10{\%}, and > 10{\%} was 65{\%}, 27{\%}, and 9{\%}, respectively. These differences were observed for patients with or without baseline BCR-ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1{\%} had an estimated 24-month EFS rate of 82{\%}, compared with 70{\%} for patients with BCR-ABL1 (IS) of > 1{\%} to ≤ 10{\%} and 48{\%} for patients with BCR-ABL1 (IS) of > 10{\%}. Conclusion: Patients with BCR-ABL1 (IS) of > 10{\%} at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10{\%}. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.",
author = "Susan Branford and Kim, {Dong Wook} and Simona Soverini and Ariful Haque and Yaping Shou and Woodman, {Richard C.} and Kantarjian, {Hagop M.} and Giovanni Martinelli and Radich, {Jerald P.} and Giuseppe Saglio and Andreas Hochhaus and Hughes, {Timothy P.} and M{\"u}ller, {Martin C.}",
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publisher = "American Society of Clinical Oncology",
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Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib. / Branford, Susan; Kim, Dong Wook; Soverini, Simona; Haque, Ariful; Shou, Yaping; Woodman, Richard C.; Kantarjian, Hagop M.; Martinelli, Giovanni; Radich, Jerald P.; Saglio, Giuseppe; Hochhaus, Andreas; Hughes, Timothy P.; Müller, Martin C.

In: Journal of Clinical Oncology, Vol. 30, No. 35, 10.12.2012, p. 4323-4329.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib

AU - Branford, Susan

AU - Kim, Dong Wook

AU - Soverini, Simona

AU - Haque, Ariful

AU - Shou, Yaping

AU - Woodman, Richard C.

AU - Kantarjian, Hagop M.

AU - Martinelli, Giovanni

AU - Radich, Jerald P.

AU - Saglio, Giuseppe

AU - Hochhaus, Andreas

AU - Hughes, Timothy P.

AU - Müller, Martin C.

PY - 2012/12/10

Y1 - 2012/12/10

N2 - Purpose: The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients and Methods: Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). Results: BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR-ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%. Conclusion: Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.

AB - Purpose: The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients and Methods: Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). Results: BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR-ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%. Conclusion: Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.

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U2 - 10.1200/JCO.2011.40.5217

DO - 10.1200/JCO.2011.40.5217

M3 - Article

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SP - 4323

EP - 4329

JO - Journal of Clinical Oncology

T2 - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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