European LeukemiaNet and National Comprehensive Cancer Network recommendations
| . | ELN optimal . | ELN warning . | ELN failure . | |
|---|---|---|---|---|
| Baseline | NA | High-risk ACA, high-risk ELTS score | NA | |
| 3 mo | ≤10% | >10% | >10% if confirmed within 1-3 mo | |
| 6 mo | ≤1% | >1%-10% | >10% | |
| 12 mo | ≤0.1% | >0.1%-1% | >1% | |
| Any time | ≤0.1% | >0.1%-1%, loss of ≤0.1% (MMR) | >1%, resistance mutations, high-risk ACA | |
| . | ELN optimal . | ELN warning . | ELN failure . | |
|---|---|---|---|---|
| Baseline | NA | High-risk ACA, high-risk ELTS score | NA | |
| 3 mo | ≤10% | >10% | >10% if confirmed within 1-3 mo | |
| 6 mo | ≤1% | >1%-10% | >10% | |
| 12 mo | ≤0.1% | >0.1%-1% | >1% | |
| Any time | ≤0.1% | >0.1%-1%, loss of ≤0.1% (MMR) | >1%, resistance mutations, high-risk ACA | |
| . | NCCN 3 months . | NCCN 6 months . | NCCN 12 months . |
|---|---|---|---|
| >10% | NCCN Possible TKI Resistance | NCCN TKI-resistant | NCCN TKI-resistant |
| >1% - 10% | NCCN TKI-sensitive | NCCN TKI-sensitive | NCCN Possible TKI Resistance |
| >0.1 - 1% | NCCN TKI-sensitive | NCCN TKI-sensitive | NCCN TKI sensitive* |
| ≤ 0.1% | NCCN TKI-sensitive | NCCN TKI-sensitive | NCCN TKI-sensitive |
| . | NCCN 3 months . | NCCN 6 months . | NCCN 12 months . |
|---|---|---|---|
| >10% | NCCN Possible TKI Resistance | NCCN TKI-resistant | NCCN TKI-resistant |
| >1% - 10% | NCCN TKI-sensitive | NCCN TKI-sensitive | NCCN Possible TKI Resistance |
| >0.1 - 1% | NCCN TKI-sensitive | NCCN TKI-sensitive | NCCN TKI sensitive* |
| ≤ 0.1% | NCCN TKI-sensitive | NCCN TKI-sensitive | NCCN TKI-sensitive |
ELN and NCCN milestone recommendations in 2020 are similar, although how each panel chooses to highlight timing of response and achievement of deeper molecular responses is slightly different. Absence of early molecular response at 6 months is considered failure by ELN recommendations and TKI resistant by NCCN recommendations. NCCN and ELN highlight achievement of <1% BCR-ABL1, which is associated with significant progression-free survival benefits. Not achieving this milestone denotes failure or TKI resistance. Both recognize that milestones such as major molecular response (MMR, BCR-ABL1 < 0.1%) must be achieved in patients aiming for treatment-free remission (TFR) and that there is a high likelihood of achieving a subsequent deep molecular response (MR4) for patients achieving MMR at 12 months. *Achievement of BCR-ABL1 >0.1-1% is associated with improved long-term overall survival even if MMR is not achieved. For ELN recommendations a change of treatment may be considered if MMR is not reached by 36 to 48 months, which may facilitate future achievement of TFR. NCCN recommendations also endorse shared decision-making with patients if MMR is not achieved. Assessment for ABL mutations are recommended for ELN warning/failure and NCCN possible TKI resistance/TKI resistance.
ACA, additional chromosome abnormalities in Philadelphia chromosome–positive cells; ELN, European LeukemiaNet; ELTS, European Treatment Outcome Study Long-Term Survival; MMR, major molecular response; NA, not applicable; NCCN, National Comprehensive Cancer Network; TKI, tyrosine kinase inhibitor.
Adapted with permission from the NCCN Guidelines® for Chronic Myeloid Leukemia V.1.2021. © 2021 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 the NCCN. 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.