Treatment-Free Remission in Chronic Myeloid Leukemia
Abstract
1. Introduction
2. TFR Eligibility
3. Strategies to Increase TFR Eligibility
4. TFR Efficacy
5. TFR Failure
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Drug Name | Notable AEs | Dose | Average Wholesale Price (USD, 2022) |
---|---|---|---|
Imatinib | Myalgias, arthralgias, skin rash, N/V/D, edema, renal insufficiency, pancreatitis | 400 mg qD | USD 564–142,000 |
Dasatinib | Pleural/pericardial effusion, PHTN, QT prolongation, bleeding | 100 mg qD | USD 228,000 |
50 mg qD | USD 127,000 | ||
20 mg qD | USD 63,000 | ||
Nilotinib | MI, peripheral arterial occlusive disease, diabetes, QT prolongation, pancreatitis, rash | 300 mg BID | USD 240,000 |
150–200 mg BID | USD 120,000 | ||
Ponatinib | HTN, HF, MI, stroke, peripheral arterial occlusive disease, arrhythmias, liver failure | 15 or 30 or 45 mg qD | USD 271,000 |
Bosutinib | N/V/D, pancreatitis, increased ALT, renal insufficiency, rash | 400 mg qD | USD 250,000 |
Asciminib | Arthralgias, dyspnea, dizziness, pancreatitis | 40 mg BID | USD 258,000 |
200 mg BID | USD 1,289,000 |
Trial | Treatment | Inclusion Criteria | Molecular Relapse Definition |
---|---|---|---|
STIM1 (n = 100) | Imatinib de novo (n = 50) or after IFN (n = 50) | UMRD for ≥2 years | Loss of UMRD |
KID (n = 90) | Imatinib de novo (n = 82) or after IFN (n = 8) | UMRD for ≥2 years | Loss of MMR |
TWISTER (n = 40) | Imatinib de novo (n = 19) or after IFN (n = 21) | UMRD for ≥2 years | Loss of UMRD |
ASTIM (n = 80) | Imatinib de novo (n = 37) or after IFN (n = 42) or cytarabine (n = 1); combined therapy (n = 15) | UMRD for ≥2 years | Loss of UMRD |
Loss of MMR | |||
ISAV (n = 108) | Imatinib de novo (n = 71) or after IFN (n = 36); 1 missing | UMRD for ≥1.5 years | Loss of MMR |
EURO-SKI (n = 755) | Frontline: Imatinib (n = 710), dasatinib (n = 14), nilotinib (n = 33), unknown (n = 1); second line: imatinib (n = 7), nilotinib (n = 47), dasatinib (n = 62) | MR4.0 for ≥1 year | Loss of MMR |
STOP 2G-TKI (n = 60) | Dasatinib (n = 30) or nilotinib (n = 30) | UMRD for ≥2 years | Loss of MMR |
ENESTFreedom (n = 190) | Nilotinib | MR4.5 for ≥1 year | Loss of MMR |
ENESTop (n = 126) | Nilotinib second line after imatinib intolerance (n = 51), imatinib resistance (n = 30) or preference for a physician (n = 45) | MR4.5 for ≥1 year | Loss of MR4 |
DADI (n = 63) | Dasatinib therapy after imatinib for resistance (n = 13), intolerance (n = 36) or a patient’s request (n = 14) | MR4.0 for ≥1 year | Loss of MR4 |
DASfree (n = 84) | Dasatinib frontline or subsequent therapy, no IFN | MR4.5 for ≥1 year | Loss of MMR |
DESTINY (n = 174) | Imatinib (n = 148), nilotinib (n = 16) or dasatinib (n = 10) | MR4.0 for ≥1 year | Loss of MMR |
MMR for ≥1 year | Loss of MMR | ||
LAST (n = 172) | Imatinib (n = 102), dasatinib (n = 27) nilotinib (n = 39) or bosutinib (n = 4) | MR4.0 for ≥2 years | Loss of MMR |
DOMEST (n = 99) | Imatinib de novo (n = 83) or after IFN (n = 16) | MR4.0 for ≥2 years | Loss of MR4 |
D-STOP (n = 54) | Dasatinib frontline (n =19) or second line: imatinib (n = 34) or unknown (n = 1) | MR4.0 for ≥2 years | Loss of MR4 |
STAT2 (n = 78) | Nilotinib second line after imatinib (n = 73) or other treatment (n = 5); after IFN (n = 12) | MR4.5 for ≥2 years | Loss of MR4.5 |
STIM2 (n = 218) | Imatinib | UMRD for ≥2 years | Loss of UMRD |
JALSG-STIM213 (n= 68) | Imatinib de novo (n = 55) or after IFN (n = 13) | MR4.0 for ≥2 years | Loss of MMR |
First-line DADI (n= 58) | Dasatinib | MR4.0 for ≥1 year | Loss of MR4 |
Trial | Predictors of Response | Patients in TFR (%) | CML Related Death Rates (%) | Progression Rates (%) | MMR Recovery Rates (%) |
---|---|---|---|---|---|
STIM1 (n = 100) | Low-risk Sokal, longer treatment duration | 38 at 60 months | 0% | 0% | 96% |
KID (n = 90) | Withdrawal syndrome, negative dPCR, longer treatment duration | 69 at 24 months | NR | NR | 100% |
TWISTER (n = 40) | Low-risk Sokal, longer duration of IFN treatment prior to TKI | 45 at 60 months | 0% | 0% | 100% |
ASTIM (n = 80) | Previous IFN treatment | 44 at 36 months (loss of UMRD) | 0% | 1% | 100% |
61 at 36 months (loss of MMR) | |||||
ISAV (n = 108) | Older age, undetectable dPCR at time of TKI discontinuation | 48 at 36 months | NR | 0% | 100% |
EURO-SKI (n = 755) | Longer treatment duration, longer MR4 prior to TKI discontinuation | 49 at 24 months | 0% | 0% | 86% |
STOP 2G-TKI (n = 60) | Prior intolerance or resistance to TKIs | 54 at 48 months | 0% | 0% | 100% |
ENESTFreedom (n = 190) | Low-risk Sokal, longer nilotinib exposure, longer MR4.5 | 49 at 96 weeks | 0% | 0% | 99% |
ENESTop (n = 126) | Longer MR4.5 duration prior to TKI discontinuation | 53 at 96 weeks | 0% | 0% | 98% |
DADI (n = 63) | Imatinib resistance, NK-cell counts, γδ+ T-cell count, CD4+ regulatory T-cell count | 44 at 36 months | NR | 0% | 100% |
DASfree (n = 84) | Older age, first-line therapy, longer treatment duration | 46 at 24 months | 0% | 0% | 96% |
DESTINY (n = 174) | Longer treatment duration, MR4 group | 72 at 36 months (MR 4.0 > 1 year) | 0% | 0% | 100% |
36 at 36 months (MMR > 1 year) | |||||
LAST (n = 172) | Undetectable RQ-PCR 3 months after TKI discontinuation, undetectable digital PCR at time of TKI discontinuation | 61 at 42 months | 0% | NR | 96% |
DOMEST (n = 99) | Longer duration of imatinib therapy, longer time from diagnosis to imatinib discontinuation, low-risk Sokal score | 64 at 24 months | NR | NR | 96% |
D-STOP (n = 54) | None | 63 at 12 months | NR | 0% | 100% |
STAT2 (n = 78) | MRD negative prior to TFR | 63 at 36 months | 0% | 0% | 100% |
STIM2 (n = 218) | NR | 50 at 24 months | NR | NR | 100% |
JALSG-STIM213 (n = 68) | UMRD before TFR | 65 at 36 months | NR | 0% | 100% |
First-line DADI (n = 58) | Lower CD4-cell count prior to dasatinib discontinuation | 55 at 12 months | NR | NR | 100% |
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Bourne, G.; Bhatia, R.; Jamy, O. Treatment-Free Remission in Chronic Myeloid Leukemia. J. Clin. Med. 2024, 13, 2567. https://doi.org/10.3390/jcm13092567
Bourne G, Bhatia R, Jamy O. Treatment-Free Remission in Chronic Myeloid Leukemia. Journal of Clinical Medicine. 2024; 13(9):2567. https://doi.org/10.3390/jcm13092567
Chicago/Turabian StyleBourne, Garrett, Ravi Bhatia, and Omer Jamy. 2024. "Treatment-Free Remission in Chronic Myeloid Leukemia" Journal of Clinical Medicine 13, no. 9: 2567. https://doi.org/10.3390/jcm13092567
APA StyleBourne, G., Bhatia, R., & Jamy, O. (2024). Treatment-Free Remission in Chronic Myeloid Leukemia. Journal of Clinical Medicine, 13(9), 2567. https://doi.org/10.3390/jcm13092567