NCCN Guidelines® recommendations for CML

Treatment of CML

NCCN Guidelines in oncology2
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 patients with CML in need of 2nd- or later-line TKI therapy (category 2A).
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020. © 2019 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 or its use or application and disclaims any responsibility for its use or application in any way.
Pfizer statement: There are no data demonstrating efficacy or safety for bosutinib in second line following dasatinib or nilotinib.
*Patients 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.
Based 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 score, especially for young women whose goal is to achieve a deep and rapid molecular response and eventual drug discontinuation of TKI therapy for family planning purposes.
Imatinib 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; 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; TKI=tyrosine kinase inhibitor.

Monitoring TKI response

NCCN Guidelines® for monitoring response in CML2
The following monitoring guidelines provide important information on monitoring the response to TKI therapy in patients with CP CML.
Early treatment response milestones*†
Monitoring with qPCR (IS) every 3 months is recommended for all patients after initiating TKI therapy, including those who meet response milestones at 3, 6, and 12 months (≤10% BCR-ABL1 IS at 3 and 6 months, ≤1% BCR-ABL1 IS at 12 months, and ≤0.1% BCR-ABL1 IS at >12 months). 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.
Treatment options based on BCR-ABL1 mutation profile2
Patients with disease resistant to primary treatment with imatinib should be treated with bosutinib, dasatinib, or nilotinib in the second-line setting, taking into account BCR-ABL1 mutation status.
Patients with disease resistant to primary treatment with bosutinib, dasatinib, or nilotinib can be treated with an alternate TKI (other than imatinib) in the second-line setting, taking into account BCR-ABL1 mutation status. The durability of these responses is frequently limited.
The table below lists the BCR-ABL1 mutations that should NOT be treated with bosutinib, dasatinib, or nilotinib in the second-line setting.
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020. © 2020 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 its use or application in any way.
For more CML monitoring guidance, please reference the full NCCN Clinical Practice Guidelines in Oncology for Chronic Myeloid Leukemia at NCCN.org.
*See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020, p CML-C, for complete details.
See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020, p CML-D, for definitions of response milestones.
BCR-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, which may facilitate discontinuation of TKI therapy.
§Patients 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.
IIAchievement of response milestones must be interpreted within the clinical context. Patients with more than 50% reduction compared with 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.
Discontinuation of TKI with careful monitoring is feasible in selected patients. See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.2.2020, p CML-E, for complete details.
#Mutations contraindicated for imatinib are too numerous to include. There are compound mutations that can cause resistance to ponatinib, but those are uncommon following treatment with bosutinib, dasatinib, or nilotinib.
**Bosutinib has minimal activity against F317L mutation. Nilotinib may be preferred over bosutinib in patients with F317L mutation.
††Ponatinib is a treatment option for patients with T315I mutation and/or patients for whom no other TKI is indicated.
‡‡Omacetaxine 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; qPCR=quantitative polymerase chain reaction; 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.3.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed April 8, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org.