You may have spotted that ELN have released their long awaited update to their guidelines for treating CML. It’s quite a long document, but I’ve given it a read and here are some of the most interesting pieces:
TFR (Treatment Free Remission).
Guidelines for TFR attempts have been long awaited, and now we have them. These are the requirements:
Mandatory:
- CML in first CP only (data are lacking outside this setting)
- Motivated patient with structured communication
- Access to high quality quantitative PCR using the International Scale (IS) with rapid turn-around of PCR test results
- Patient’s agreement to more frequent monitoring after stopping treatment. This means monthly for the first 6 months, every 2 months for months 6–12, and every 3 months thereafter.
Minimal (stop allowed):
- First-line therapy or second-line if intolerance was the only reason for changing TKI
- Typical e13a2 or e14a2 BCR–ABL1 transcripts
- Duration of TKI therapy >5 years (>4 years for 2GTKI)
- Duration of DMR (MR4 or better) >2 years
- No prior treatment failure
Optimal (stop recommended for consideration):
- Duration of TKI therapy >5 years
- Duration of DMR > 3 years if MR4
- Duration of DMR > 2 years if MR4.5
Fertility:
Men: For men taking imatinib, bosutinib, dasatinib, or nilotinib, there is no increased risk of congenital abnormalities in their offspring. Data are sparse/absent for ponatinib and asciminib, respectively. Changes in sperm quality and morphology can be present at diagnosis and are unchanged after imatinib. Therefore, men planning fatherhood do not need to discontinue treatment with imatinib or 2GTKI.
Women: Confirmation that TKIs are contraindicated during pregnancy. For women, management of CML occurring during pregnancy must be individualized. TKI treatment should be discontinued in the first trimester, as soon as pregnancy is confirmed. Interferon-alpha could be given in some cases to manage CML whilst pregnant.
Milestones:
OptimalWarningFailureBaselineN/AHigh-risk ACA, high-risk ELTS scoreN/A3 Months≤10%>10%>10% if confirmed within 1–3 months6 Months≤1%>1-10%>10%12 Months≤0.1%>0.1-1%>1%Any Time≤0.1%>0.1-1%, loss of MMR>1%, resistance mutations, high-risk ACA
Prognostic Scoring:
The EUTOS Long Term Survival prognostic scoring method is preferred over others, such as Sokal or Hasford. You can calculate your score here, but you will need some details of your prognostic factors at diagnosis:
https://www.leukemia-net.org/content/leukemias/cml/elts_score/index_eng....
Full guidance here: