Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors

Ahmad Alhuraiji, Hagop Kantarjian, Prajwal Boddu, Farhad Ravandi, Gautam Borthakur, Courtney DiNardo, Naval Daver, Tapan Kadia, Naveen Pemmaraju, Sherry Pierce, Guillermo Garcia-Manero, William Wierda, Srdan Verstovsek, Elias Jabbour, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148 (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with ponatinib. There was a significantly higher rate of complete cytogenetic response (CCyR) at 6 months in patients without ACA (P =.02). However cumulative CCyR and major molecular response (MMR) rates were not different. Similarly, MR4.0 and MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5 for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact transformation-free, failure-free, event-free, or overall survival expectations. Acknowledging small sample size estimates, response rates and survival outcomes were comparable in CP with ACA irrespective of whether chromosomal abnormalities were “major route” or other. The presence of ACA at diagnosis does not confer worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA at diagnosis should not alter treatment strategies in these patients.

Original languageEnglish (US)
Pages (from-to)84-90
Number of pages7
JournalAmerican Journal of Hematology
Volume93
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosome Aberrations
Protein-Tyrosine Kinases
Cytogenetics
Sample Size
Survival Rate
Clinical Trials
Survival

ASJC Scopus subject areas

  • Hematology

Cite this

Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors. / Alhuraiji, Ahmad; Kantarjian, Hagop; Boddu, Prajwal; Ravandi, Farhad; Borthakur, Gautam; DiNardo, Courtney; Daver, Naval; Kadia, Tapan; Pemmaraju, Naveen; Pierce, Sherry; Garcia-Manero, Guillermo; Wierda, William; Verstovsek, Srdan; Jabbour, Elias; Cortes, Jorge.

In: American Journal of Hematology, Vol. 93, No. 1, 01.2018, p. 84-90.

Research output: Contribution to journalArticle

Alhuraiji, A, Kantarjian, H, Boddu, P, Ravandi, F, Borthakur, G, DiNardo, C, Daver, N, Kadia, T, Pemmaraju, N, Pierce, S, Garcia-Manero, G, Wierda, W, Verstovsek, S, Jabbour, E & Cortes, J 2018, 'Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors', American Journal of Hematology, vol. 93, no. 1, pp. 84-90. https://doi.org/10.1002/ajh.24943
Alhuraiji, Ahmad ; Kantarjian, Hagop ; Boddu, Prajwal ; Ravandi, Farhad ; Borthakur, Gautam ; DiNardo, Courtney ; Daver, Naval ; Kadia, Tapan ; Pemmaraju, Naveen ; Pierce, Sherry ; Garcia-Manero, Guillermo ; Wierda, William ; Verstovsek, Srdan ; Jabbour, Elias ; Cortes, Jorge. / Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors. In: American Journal of Hematology. 2018 ; Vol. 93, No. 1. pp. 84-90.
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AU - Kantarjian, Hagop

AU - Boddu, Prajwal

AU - Ravandi, Farhad

AU - Borthakur, Gautam

AU - DiNardo, Courtney

AU - Daver, Naval

AU - Kadia, Tapan

AU - Pemmaraju, Naveen

AU - Pierce, Sherry

AU - Garcia-Manero, Guillermo

AU - Wierda, William

AU - Verstovsek, Srdan

AU - Jabbour, Elias

AU - Cortes, Jorge

PY - 2018/1

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N2 - Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148 (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with ponatinib. There was a significantly higher rate of complete cytogenetic response (CCyR) at 6 months in patients without ACA (P =.02). However cumulative CCyR and major molecular response (MMR) rates were not different. Similarly, MR4.0 and MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5 for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact transformation-free, failure-free, event-free, or overall survival expectations. Acknowledging small sample size estimates, response rates and survival outcomes were comparable in CP with ACA irrespective of whether chromosomal abnormalities were “major route” or other. The presence of ACA at diagnosis does not confer worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA at diagnosis should not alter treatment strategies in these patients.

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