A comparison of the classification of the response in the first-line setting, with the ELN 2013 and the NCCN 1.2019 classifications
| . | Optimal . | Warning or nonoptimal . | Failure . | ||||||
|---|---|---|---|---|---|---|---|---|---|
| ELN 2013 . | GIMEMA 2019 . | NCCN 1.2019 . | ELN 2013 . | GIMEMA 2019 . | NCCN 1.2019 . | ELN 2013 . | GIMEMA 2019 . | NCCN 1.2019 . | |
| Baseline | NA | NA | NA | High risk, or CCA/Ph+, major route | NA | NA | NA | NA | NA |
| 3 mo | BCR-ABL1 ≤10% or Ph+ ≤35% | BCR-ABL1 ≤10% or BCR-ABL1 >10%, not confirmed | BCR-ABL1 <10% | BCR-ABL1 >10%, or Ph+ 35%-95% | NA | BCR-ABL1 >10% | No CHR, or Ph+ >95% | No CHR, or BCR-ABL1 >10% confirmed | NA |
| 6 mo | BCR-ABL ≤1% or Ph+ 0 | BCR-ABL1 ≤1% | BCR-ABL1 <10% | BCR-ABL1 1%-10% or Ph+ 1%-35% | BCR-ABL1 >1%-10% | NA | BCR-ABL1 >10% or Ph+ >35% | BCR-ABL1 >10% | BCR-ABL1 >10% |
| 12 mo | BCR-ABL1 ≤0.1% | BCR-ABL1 ≤0.1% | BCR-ABL1 ≤1% | BCR-ABL1 0.1%-1% | BCR-ABL1 >0.1%-1% | BCR-ABL1 >1%-10% | BCR-ABL1 >1% or Ph+ >0 | BCR-ABL1 >1% | BCR-ABL1 >10% |
| Then* | BCR-ABL1 ≤0.1% | BCR-ABL1 ≤0.01% | BCR-ABL1 ≤1% | CCA/Ph− (−7, 7q−) | BCR-ABL1 >0.01%-0.1% | NA | Loss of CHR, or CCyR, or MMR, or mutations, or CCA/Ph+ | BCR-ABL1 >0.1% or mutations, or BCR-ABL1 increase of >1 log | BCR-ABL1 >1% |
| . | Optimal . | Warning or nonoptimal . | Failure . | ||||||
|---|---|---|---|---|---|---|---|---|---|
| ELN 2013 . | GIMEMA 2019 . | NCCN 1.2019 . | ELN 2013 . | GIMEMA 2019 . | NCCN 1.2019 . | ELN 2013 . | GIMEMA 2019 . | NCCN 1.2019 . | |
| Baseline | NA | NA | NA | High risk, or CCA/Ph+, major route | NA | NA | NA | NA | NA |
| 3 mo | BCR-ABL1 ≤10% or Ph+ ≤35% | BCR-ABL1 ≤10% or BCR-ABL1 >10%, not confirmed | BCR-ABL1 <10% | BCR-ABL1 >10%, or Ph+ 35%-95% | NA | BCR-ABL1 >10% | No CHR, or Ph+ >95% | No CHR, or BCR-ABL1 >10% confirmed | NA |
| 6 mo | BCR-ABL ≤1% or Ph+ 0 | BCR-ABL1 ≤1% | BCR-ABL1 <10% | BCR-ABL1 1%-10% or Ph+ 1%-35% | BCR-ABL1 >1%-10% | NA | BCR-ABL1 >10% or Ph+ >35% | BCR-ABL1 >10% | BCR-ABL1 >10% |
| 12 mo | BCR-ABL1 ≤0.1% | BCR-ABL1 ≤0.1% | BCR-ABL1 ≤1% | BCR-ABL1 0.1%-1% | BCR-ABL1 >0.1%-1% | BCR-ABL1 >1%-10% | BCR-ABL1 >1% or Ph+ >0 | BCR-ABL1 >1% | BCR-ABL1 >10% |
| Then* | BCR-ABL1 ≤0.1% | BCR-ABL1 ≤0.01% | BCR-ABL1 ≤1% | CCA/Ph− (−7, 7q−) | BCR-ABL1 >0.01%-0.1% | NA | Loss of CHR, or CCyR, or MMR, or mutations, or CCA/Ph+ | BCR-ABL1 >0.1% or mutations, or BCR-ABL1 increase of >1 log | BCR-ABL1 >1% |
ELN 2013 and the NCCN 1.2019 classifications.9,34 Notice that for the GIMEMA classification it is mandatory to repeat immediately the qPCR if at 3 months the BCR-ABL1 level is >10%. If the BCR-ABL1 level drops to ≤10%, the response turns to optimal. If it is confirmed to be >10%, the response turns to failure/resistance. Therefore, the GIMEMA classification does not foresee a “nonoptimal” response at 3 months. The cost of an extra qPCR not only allows the patient to make the best choice, but is also fully covered by the cost differences between imatinib and 2GTKIs. At baseline, high-risk and clonal chromosome abnormalities (CCA)/Ph+ are no longer classified as “warning” because they are included in the high-risk treatment group. The ELN term “warning” is substituted by the term “nonoptimal.” This is not a trivial difference because the meaning of “warning” was “be careful and monitor the response more frequently,” whereas “nonoptimal” means that it opens an option for a switch, depending not only on the response but also on the patients (age, health conditions, comorbidities, quality of life, etc). At 6 and 12 months, the GIMEMA and ELN 2013 classifications are identical. After 12 months, the GIMEMA panel has agreed on more stringent definitions of optimal response, from BCR-ABL1 ≤0.1% to BCR-ABL1 ≤0.01% for optimal response, and from BCR-ABL >1% to BCR-ABL1 >0.1% for failure. The 1.2019 NCCN criteria are much less stringent because after 1 year (at 15 months) only a BCR-ABL1 level >1% mandates a change of treatment. Notice that GIMEMA definitions refer to TFR, whereas ELN and NCCN definitions refer to survival.
At any time for ELN 2013, at 24 months for GIMEMA, at 15 months for NCCN 1.2019.