Outcomes of Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Following an Elective Switch From Second-Generation Tyrosine Kinase Inhibitor to Imatinib

Vamsi Kota, Jee Hyun Kong, Martha Arellano, Fuad El Rassi, Manila Gaddh, Leonard T. Heffner, Elliott F. Winton, Anand Jillella, Morgan L. McLemore, H. Jean Khoury

Research output: Contribution to journalComment/debate

1 Citation (Scopus)

Abstract

The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term safety of these agents is a growing concern. We identified 20 patients with CP-CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. Second-generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1). One other patient initiated therapy with ponatinib on trial. Response was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) for BCR-ABL1 levels every 3 months and in patients with qRT-PCR values less than 10% at 3 months, IM was started at 400 mg/d. IM was well tolerated except in 2 patients who required dose-reduction and discontinuation due to grade 2 skin rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR-ABL1 qRT-PCR levels trended down as expected. At 12 months 16 (84.2%) of 19 evaluable patients showed a 3 log (major molecular remission) or better reduction in their PCR levels. In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G-TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.

Original languageEnglish (US)
Pages (from-to)e71-e73
JournalClinical Lymphoma, Myeloma and Leukemia
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Protein-Tyrosine Kinases
Reverse Transcriptase Polymerase Chain Reaction
Safety
Exanthema
Imatinib Mesylate
Therapeutics
Anxiety
Polymerase Chain Reaction

Keywords

  • Dasatinib
  • Early response
  • Imatinib
  • Nilotinib
  • TKI safety

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Outcomes of Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Following an Elective Switch From Second-Generation Tyrosine Kinase Inhibitor to Imatinib. / Kota, Vamsi; Kong, Jee Hyun; Arellano, Martha; El Rassi, Fuad; Gaddh, Manila; Heffner, Leonard T.; Winton, Elliott F.; Jillella, Anand; McLemore, Morgan L.; Khoury, H. Jean.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 17, No. 12, 01.12.2017, p. e71-e73.

Research output: Contribution to journalComment/debate

Kota, Vamsi ; Kong, Jee Hyun ; Arellano, Martha ; El Rassi, Fuad ; Gaddh, Manila ; Heffner, Leonard T. ; Winton, Elliott F. ; Jillella, Anand ; McLemore, Morgan L. ; Khoury, H. Jean. / Outcomes of Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Following an Elective Switch From Second-Generation Tyrosine Kinase Inhibitor to Imatinib. In: Clinical Lymphoma, Myeloma and Leukemia. 2017 ; Vol. 17, No. 12. pp. e71-e73.
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abstract = "The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term safety of these agents is a growing concern. We identified 20 patients with CP-CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. Second-generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1). One other patient initiated therapy with ponatinib on trial. Response was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) for BCR-ABL1 levels every 3 months and in patients with qRT-PCR values less than 10{\%} at 3 months, IM was started at 400 mg/d. IM was well tolerated except in 2 patients who required dose-reduction and discontinuation due to grade 2 skin rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR-ABL1 qRT-PCR levels trended down as expected. At 12 months 16 (84.2{\%}) of 19 evaluable patients showed a 3 log (major molecular remission) or better reduction in their PCR levels. In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G-TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.",
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AU - Kota, Vamsi

AU - Kong, Jee Hyun

AU - Arellano, Martha

AU - El Rassi, Fuad

AU - Gaddh, Manila

AU - Heffner, Leonard T.

AU - Winton, Elliott F.

AU - Jillella, Anand

AU - McLemore, Morgan L.

AU - Khoury, H. Jean

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term safety of these agents is a growing concern. We identified 20 patients with CP-CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. Second-generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1). One other patient initiated therapy with ponatinib on trial. Response was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) for BCR-ABL1 levels every 3 months and in patients with qRT-PCR values less than 10% at 3 months, IM was started at 400 mg/d. IM was well tolerated except in 2 patients who required dose-reduction and discontinuation due to grade 2 skin rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR-ABL1 qRT-PCR levels trended down as expected. At 12 months 16 (84.2%) of 19 evaluable patients showed a 3 log (major molecular remission) or better reduction in their PCR levels. In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G-TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.

AB - The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term safety of these agents is a growing concern. We identified 20 patients with CP-CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. Second-generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1). One other patient initiated therapy with ponatinib on trial. Response was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) for BCR-ABL1 levels every 3 months and in patients with qRT-PCR values less than 10% at 3 months, IM was started at 400 mg/d. IM was well tolerated except in 2 patients who required dose-reduction and discontinuation due to grade 2 skin rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR-ABL1 qRT-PCR levels trended down as expected. At 12 months 16 (84.2%) of 19 evaluable patients showed a 3 log (major molecular remission) or better reduction in their PCR levels. In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G-TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.

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KW - Early response

KW - Imatinib

KW - Nilotinib

KW - TKI safety

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