Does the frequency of molecular monitoring after tyrosine kinase inhibitor discontinuation affect outcomes of patients with chronic myeloid leukemia?

Jee Hyun Kong, Elliott F. Winton, Leonard T. Heffner, Zhengjia Chen, Amelia A. Langston, Brittany Hill, Martha Arellano, Fuad El-Rassi, Audrey Kim, Anand Jillella, Vamsi Kota, Imre Bodó, Hanna Jean Khoury

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND: To the authors' knowledge, the optimal frequency of monitoring after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic myeloid leukemia (CML) has not been established. Data regarding the discontinuation of second-generation TKIs used in first-line treatment or after the failure of first-line treatment with TKIs are limited. Herein, the authors report real-world experience with “reduced frequency” molecular monitoring in patients with CML in all phases who discontinued treatment with imatinib, dasatinib, or bosutinib. METHODS: The records of patients who discontinued TKIs were reviewed. Patients who discontinued TKIs were monitored prospectively on an intended schedule of monthly blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 for 3 months, quarterly for 12 months, and every 6 months thereafter until loss of major molecular response (MMR). After loss of MMR, the TKI that previously was discontinued was reinitiated. RESULTS: Between January 2010 and September 2015, a total of 24 patients in chronic (21 patients), accelerated (2 patients), and lymphoid blast (1 patient) phase discontinued imatinib (16 patients), dasatinib (5 patients), or bosutinib (3 patients) used in the front-line treatment or beyond. Blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 was performed 1.3 ± 0.7 times within the first 3 months (24 patients) and 2.7 ± 1.4 times in the following 12 months (18 patients). With a median follow-up of 36.5 months (range, 3.2-67.4 months), the probabilities of treatment-free remission at 1 year and 2 years were 65.7% (95% confidence interval, 55.8%-75.6%) and 59.7% (95% confidence interval, 49.1%-70.3%), respectively. Loss of MMR was observed in 9 patients at a median of 2.8 months (range, 1.8-14.2 months) after discontinuation of TKIs. CONCLUSIONS: With the limitations of a small sample size, the results of the current study demonstrate that less frequent monitoring of BCR-ABL1 does not appear to affect outcomes, and that discontinuation of TKIs used as first-line treatment or beyond after resistance or intolerance to first-line treatment appears feasible. Cancer 2017;123:2482–88.

Original languageEnglish (US)
Pages (from-to)2482-2488
Number of pages7
JournalCancer
Volume123
Issue number13
DOIs
StatePublished - Jul 1 2017

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Reverse Transcriptase Polymerase Chain Reaction
Therapeutics
Confidence Intervals
Physiologic Monitoring
Sample Size
Appointments and Schedules

Keywords

  • BCR/ABL1
  • chronic myeloid leukemia
  • discontinuation
  • monitoring
  • tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kong, J. H., Winton, E. F., Heffner, L. T., Chen, Z., Langston, A. A., Hill, B., ... Khoury, H. J. (2017). Does the frequency of molecular monitoring after tyrosine kinase inhibitor discontinuation affect outcomes of patients with chronic myeloid leukemia? Cancer, 123(13), 2482-2488. https://doi.org/10.1002/cncr.30608

Does the frequency of molecular monitoring after tyrosine kinase inhibitor discontinuation affect outcomes of patients with chronic myeloid leukemia? / Kong, Jee Hyun; Winton, Elliott F.; Heffner, Leonard T.; Chen, Zhengjia; Langston, Amelia A.; Hill, Brittany; Arellano, Martha; El-Rassi, Fuad; Kim, Audrey; Jillella, Anand; Kota, Vamsi; Bodó, Imre; Khoury, Hanna Jean.

In: Cancer, Vol. 123, No. 13, 01.07.2017, p. 2482-2488.

Research output: Contribution to journalArticle

Kong, JH, Winton, EF, Heffner, LT, Chen, Z, Langston, AA, Hill, B, Arellano, M, El-Rassi, F, Kim, A, Jillella, A, Kota, V, Bodó, I & Khoury, HJ 2017, 'Does the frequency of molecular monitoring after tyrosine kinase inhibitor discontinuation affect outcomes of patients with chronic myeloid leukemia?', Cancer, vol. 123, no. 13, pp. 2482-2488. https://doi.org/10.1002/cncr.30608
Kong, Jee Hyun ; Winton, Elliott F. ; Heffner, Leonard T. ; Chen, Zhengjia ; Langston, Amelia A. ; Hill, Brittany ; Arellano, Martha ; El-Rassi, Fuad ; Kim, Audrey ; Jillella, Anand ; Kota, Vamsi ; Bodó, Imre ; Khoury, Hanna Jean. / Does the frequency of molecular monitoring after tyrosine kinase inhibitor discontinuation affect outcomes of patients with chronic myeloid leukemia?. In: Cancer. 2017 ; Vol. 123, No. 13. pp. 2482-2488.
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abstract = "BACKGROUND: To the authors' knowledge, the optimal frequency of monitoring after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic myeloid leukemia (CML) has not been established. Data regarding the discontinuation of second-generation TKIs used in first-line treatment or after the failure of first-line treatment with TKIs are limited. Herein, the authors report real-world experience with “reduced frequency” molecular monitoring in patients with CML in all phases who discontinued treatment with imatinib, dasatinib, or bosutinib. METHODS: The records of patients who discontinued TKIs were reviewed. Patients who discontinued TKIs were monitored prospectively on an intended schedule of monthly blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 for 3 months, quarterly for 12 months, and every 6 months thereafter until loss of major molecular response (MMR). After loss of MMR, the TKI that previously was discontinued was reinitiated. RESULTS: Between January 2010 and September 2015, a total of 24 patients in chronic (21 patients), accelerated (2 patients), and lymphoid blast (1 patient) phase discontinued imatinib (16 patients), dasatinib (5 patients), or bosutinib (3 patients) used in the front-line treatment or beyond. Blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 was performed 1.3 ± 0.7 times within the first 3 months (24 patients) and 2.7 ± 1.4 times in the following 12 months (18 patients). With a median follow-up of 36.5 months (range, 3.2-67.4 months), the probabilities of treatment-free remission at 1 year and 2 years were 65.7{\%} (95{\%} confidence interval, 55.8{\%}-75.6{\%}) and 59.7{\%} (95{\%} confidence interval, 49.1{\%}-70.3{\%}), respectively. Loss of MMR was observed in 9 patients at a median of 2.8 months (range, 1.8-14.2 months) after discontinuation of TKIs. CONCLUSIONS: With the limitations of a small sample size, the results of the current study demonstrate that less frequent monitoring of BCR-ABL1 does not appear to affect outcomes, and that discontinuation of TKIs used as first-line treatment or beyond after resistance or intolerance to first-line treatment appears feasible. Cancer 2017;123:2482–88.",
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AU - Kong, Jee Hyun

AU - Winton, Elliott F.

AU - Heffner, Leonard T.

AU - Chen, Zhengjia

AU - Langston, Amelia A.

AU - Hill, Brittany

AU - Arellano, Martha

AU - El-Rassi, Fuad

AU - Kim, Audrey

AU - Jillella, Anand

AU - Kota, Vamsi

AU - Bodó, Imre

AU - Khoury, Hanna Jean

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N2 - BACKGROUND: To the authors' knowledge, the optimal frequency of monitoring after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic myeloid leukemia (CML) has not been established. Data regarding the discontinuation of second-generation TKIs used in first-line treatment or after the failure of first-line treatment with TKIs are limited. Herein, the authors report real-world experience with “reduced frequency” molecular monitoring in patients with CML in all phases who discontinued treatment with imatinib, dasatinib, or bosutinib. METHODS: The records of patients who discontinued TKIs were reviewed. Patients who discontinued TKIs were monitored prospectively on an intended schedule of monthly blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 for 3 months, quarterly for 12 months, and every 6 months thereafter until loss of major molecular response (MMR). After loss of MMR, the TKI that previously was discontinued was reinitiated. RESULTS: Between January 2010 and September 2015, a total of 24 patients in chronic (21 patients), accelerated (2 patients), and lymphoid blast (1 patient) phase discontinued imatinib (16 patients), dasatinib (5 patients), or bosutinib (3 patients) used in the front-line treatment or beyond. Blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 was performed 1.3 ± 0.7 times within the first 3 months (24 patients) and 2.7 ± 1.4 times in the following 12 months (18 patients). With a median follow-up of 36.5 months (range, 3.2-67.4 months), the probabilities of treatment-free remission at 1 year and 2 years were 65.7% (95% confidence interval, 55.8%-75.6%) and 59.7% (95% confidence interval, 49.1%-70.3%), respectively. Loss of MMR was observed in 9 patients at a median of 2.8 months (range, 1.8-14.2 months) after discontinuation of TKIs. CONCLUSIONS: With the limitations of a small sample size, the results of the current study demonstrate that less frequent monitoring of BCR-ABL1 does not appear to affect outcomes, and that discontinuation of TKIs used as first-line treatment or beyond after resistance or intolerance to first-line treatment appears feasible. Cancer 2017;123:2482–88.

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KW - BCR/ABL1

KW - chronic myeloid leukemia

KW - discontinuation

KW - monitoring

KW - tyrosine kinase inhibitor

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