Recommendations for TFR
| Parameter . | European LeukemiaNet 20205 . | National Comprehensive Cancer Network 202138 . | French Chronic Myeloid Leukemia Study Group 201839 . |
|---|---|---|---|
| Mandatory | |||
| Age, phase of the disease, disease history | Adult patients, CML in first chronic phase only. No prior treatment failure. | Age ≥18 years. Chronic-phase CML. No prior history of accelerated or blast-phase CML. | Age ≥18 years. Chronic-phase CML. No prior history of allogeneic stem cell transplantation, progression, resistance, suboptimal response, or warning. |
| Motivation, communication, information | Motivated patient with structured communication. Patient's acceptance of more frequent PCR tests after stopping treatment. | Consultation with a CML specialist to review eligibility for TKI discontinuation and potential risks and benefits of treatment discontinuation, including TKI withdrawal syndrome. Discontinuation of TKI therapy should only be performed in consenting patients after a thorough discussion of the potential risks and benefits. | Adherence to monitoring and retreatment recommendations. Written information and instructions may be provided. |
| Molecular-monitoring infrastructure | Access to high-quality qRT-PCR using the IS with rapid turnaround of PCR test results | Access to a reliable quantitative PCR test with a sensitivity of detection of at least MR4.5 (BCR-ABL1 ≤ 0.0032% IS) that provides results within 2 weeks. | Results should be available within 2-3 weeks. Molecular biologists should be aware of TKI discontinuations in individual patients. |
| Molecular-monitoring frequency | Monthly molecular monitoring for the first 6 months, bimonthly during months 7-12, and quarterly thereafter (indefinitely) | Monthly during the first half year, every 2 months. In the second half year, quarterly during the second year and then every 3 to 6 months. | |
| Minimal (stop allowed) | |||
| Line of treatment | First-line or second-line therapy if intolerance was the only reason for changing TKI | ||
| BCR-ABL1 transcript type | Typical e13a2 or e14a2 BCR-ABL1 transcripts | Prior evidence of a quantifiable BCR-ABL1 transcript | BCR-ABL1 transcripts e13a2, e14a2, or e13a2/e14a2 |
| Duration of TKI therapy | Duration of TKI therapy >5 years (>4 years for second-generation TKI) | On approved TKI therapy for at least 3 years | TKI treatment duration ≥5 years. |
| Duration of DMR | DMR (MR4 or better) for >2 years | Stable MR (MR4; BCR-ABL1 ≤ 0.01% IS) for ≥2 years, as documented on at least 4 tests, performed at least 3 mo apart. | DMR at least MR4.5. DMR duration ≥2 years. MR4.5 is confirmed in ≥4 consecutive tests. At most 1 of the 4 assessments showing an MR4 is accepted. |
| 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 | |||
| Parameter . | European LeukemiaNet 20205 . | National Comprehensive Cancer Network 202138 . | French Chronic Myeloid Leukemia Study Group 201839 . |
|---|---|---|---|
| Mandatory | |||
| Age, phase of the disease, disease history | Adult patients, CML in first chronic phase only. No prior treatment failure. | Age ≥18 years. Chronic-phase CML. No prior history of accelerated or blast-phase CML. | Age ≥18 years. Chronic-phase CML. No prior history of allogeneic stem cell transplantation, progression, resistance, suboptimal response, or warning. |
| Motivation, communication, information | Motivated patient with structured communication. Patient's acceptance of more frequent PCR tests after stopping treatment. | Consultation with a CML specialist to review eligibility for TKI discontinuation and potential risks and benefits of treatment discontinuation, including TKI withdrawal syndrome. Discontinuation of TKI therapy should only be performed in consenting patients after a thorough discussion of the potential risks and benefits. | Adherence to monitoring and retreatment recommendations. Written information and instructions may be provided. |
| Molecular-monitoring infrastructure | Access to high-quality qRT-PCR using the IS with rapid turnaround of PCR test results | Access to a reliable quantitative PCR test with a sensitivity of detection of at least MR4.5 (BCR-ABL1 ≤ 0.0032% IS) that provides results within 2 weeks. | Results should be available within 2-3 weeks. Molecular biologists should be aware of TKI discontinuations in individual patients. |
| Molecular-monitoring frequency | Monthly molecular monitoring for the first 6 months, bimonthly during months 7-12, and quarterly thereafter (indefinitely) | Monthly during the first half year, every 2 months. In the second half year, quarterly during the second year and then every 3 to 6 months. | |
| Minimal (stop allowed) | |||
| Line of treatment | First-line or second-line therapy if intolerance was the only reason for changing TKI | ||
| BCR-ABL1 transcript type | Typical e13a2 or e14a2 BCR-ABL1 transcripts | Prior evidence of a quantifiable BCR-ABL1 transcript | BCR-ABL1 transcripts e13a2, e14a2, or e13a2/e14a2 |
| Duration of TKI therapy | Duration of TKI therapy >5 years (>4 years for second-generation TKI) | On approved TKI therapy for at least 3 years | TKI treatment duration ≥5 years. |
| Duration of DMR | DMR (MR4 or better) for >2 years | Stable MR (MR4; BCR-ABL1 ≤ 0.01% IS) for ≥2 years, as documented on at least 4 tests, performed at least 3 mo apart. | DMR at least MR4.5. DMR duration ≥2 years. MR4.5 is confirmed in ≥4 consecutive tests. At most 1 of the 4 assessments showing an MR4 is accepted. |
| 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 | |||