NCCN Guidelines® treatment recommendations and response monitoring in CML

Treatment of CML

NCCN Guidelines2
Bosutinib (BOSULIF) is recommended by the NCCN Guidelines as a primary treatment option for patients with newly diagnosed CP-CML (category 1) and as an option for CML patients in need of 2nd- or later-line TKI therapy.
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2019. © 2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Pfizer Statement: There are no data demonstrating efficacy or safety for bosutinib in second line following dasatinib or nilotinib.
aPatients with disease that is resistant to primary treatment with imatinib should be treated with bosutinib, dasatinib, or nilotinib in the second-line setting. Patients with disease that is resistant to primary treatment with bosutinib, dasatinib, or nilotinib could be treated with an alternate TKI (other than imatinib) in the second-line setting, based on BCR-ABL1 mutation profile.
bqPCR (IS) is the preferred method to monitor response to TKI therapy. If qPCR (IS) is not available, it is acceptable to use the log-reduction from the laboratory-specific standardized baseline to monitor response. Monitoring with qPCR (IS) every 3 months is recommended for all patients. After CCyR (≤1% BCR-ABL1 IS) has been achieved, molecular monitoring is recommended every 3 months for 2 years and every 3 to 6 months thereafter.
cBased on long-term follow-up data from the DASISION and ENESTnd trials and preliminary data from the BFORE trial, second-generation TKIs (dasatinib, nilotinib, or bosutinib) are preferred for patients with an intermediate- or high-risk Sokal or Hasford score, especially for young women whose goal is to achieve a deep and rapid molecular response and eventual drug discontinuation of TKI therapy for fertility purposes.
dImatinib may be preferred for older patients with comorbidities such as cardiovascular disease.
BCR-ABL=breakpoint cluster region-Abelson; BFORE=Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment; CCyR=complete cytogenetic response; DASISION=The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients; ENESTnd=Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients; NCCN=National Comprehensive Cancer Network; Ph+=Philadelphia chromosome–positive; qPCR=quantitative RT-PCR; TKI=tyrosine kinase inhibitor.
References
1.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
2.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2019. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed August 20, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. 

Monitoring TKI response

NCCN Guidelines Recommendations for monitoring response in CML2
The following monitoring Guidelines provide important information on monitoring the response to TKI therapy in patients with chronic phase (CP) CML.
Early Treatment Response Milestones2,a,b
Monitoring with quantitative polymerase chain reaction (qPCR) using IS every 3 months is recommended for all patients after initiating therapy, including those who meet response milestones at 3, 6, and 12 months, and beyond. After BCR-ABL1 >0.1%-1% (IS) has been achieved, molecular monitoring is recommended every 3 months for 2 years and every 3 to 6 months thereafter.2
Treatment options based on BCR-ABL1 mutation profile2
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2019. © 2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
For more CML monitoring guidance, please reference the full NCCN Guidelines for Chronic Myeloid Leukemia V.1.2019.
aSee NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2019, p CML-C, for complete details.
bSee NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2019, p CML-D, for definitions of response milestones.
cPatients with BCR-ABL1 only slightly >10% at 3 months and/or with a steep decline from baseline may achieve <10% at 6 months and have generally favorable outcomes. Therefore, it is important to interpret the value at 3 months in this context before making drastic changes to the treatment strategy.
dBCR-ABL1 0.1% at 12 months is associated with a very low probability of subsequent disease progression and a high likelihood of achieving a subsequent MR4.0, which may facilitate discontinuation of TKI therapy.
eAchievement of response milestones must be interpreted within the clinical context. Patients with more than 50% reduction compared to baseline or minimally above the 10% cutoff can continue the same dose of dasatinib, nilotinib, or bosutinib for another 3 months. Continuation of imatinib 400 mg is not recommended.
fDiscontinuation of TKI with careful monitoring is feasible in selected patients. See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2019, p CML-E, for complete details.
gPatients with disease that is resistant to primary treatment with imatinib should be treated with bosutinib, dasatinib, or nilotinib in the second-line setting. Patients with disease that is resistant to primary treatment with bosutinib, dasatinib, or nilotinib could be treated with an alternate TKI (other than imatinib) in the second-line setting.
hPonatinib is a treatment option for patients with a T315I mutation or for patients for whom no other TKI is indicated.
iOmacetaxine is a treatment option for patients with disease that is resistant and/or intolerant to 2 or more TKIs.
BCR-ABL=breakpoint cluster region-Abelson; CCyR=complete cytogenetic response; HCT=hematopoietic stem cell transplant; IS=International Scale; MCyR=major cytogenetic response; NCCN=National Comprehensive Cancer Network; Ph+=Philadelphia chromosome–positive; TKI=tyrosine kinase inhibitor.
References
1.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
2.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2019. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed August 20, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.