A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia
Abstract
:1. Introduction
2. Patients and Methods
2.1. Study Population
2.2. Ponatinib Plasma Concentration Measures
2.3. Ponatinib Pharmacokinetic Study
2.4. Molecular Response Evaluation and BCR-ABL1 Mutation Analysis
2.5. Statistical Analysis
3. Results
3.1. Study Population: Clinical Features and Outcome
3.2. PON Plasma Concentrations
3.3. PON Daily Dose, Plasma Concentrations, Molecular Responses, and AE
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number | Percentage | ||
---|---|---|---|
Number of pts | 32 | / | |
Sex | Male | 16 | 50% |
Female | 16 | 50% | |
Age (years) | Median | 56.5 | / |
Range | 22–71 | / | |
Risk score at diagnosis (Sokal) | Low | 11 | 34.4% |
Intermediate | 14 | 43.7% | |
High | 7 | 21.9% | |
Cause of switch to PON | Resistance | 18 | 56.2% |
Toxicity | 14 | 43.8% | |
Previous lines of treatment | 1 | 17 | 53.1% |
2 | 11 | 34.4% | |
>2 | 4 | 12.5% | |
PON daily dose (mg) | 45 | 9 | 23.7% |
30 | 17 | 44.7% | |
15 | 12 | 31.6% | |
Best molecular response (38 assessments) | <MR3 1 | 13 | 34.2% |
MR3 | 25 | 65.7% | |
DMR | 20 | 52.6% | |
Adverse Events (grade 3–4) | Hematological | 5 | 15.6% |
Extra-hematological | 8 | 25% |
Threshold of PON Plasma Concentration | Cmin 1 | MR3 | DMR |
---|---|---|---|
10.7 ng/mL | Higher than | 9/11 (81.8%) | 10/27 (37.0%) |
Lower than | 16/27 (81.8%) | 5/11 (45.5%) | |
21.3 ng/mL | Higher than | 6/25 (24.0%) | 5/15 (33.3%) |
Lower than | 19/25 (76%) | 10/15 (66.6%) |
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Galimberti, S.; Abruzzese, E.; Luci, G.; Baratè, C.; Luciano, L.; Iurlo, A.; Caocci, G.; Morganti, R.; Stefanelli, F.; Di Paolo, A. A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia. Pharmaceutics 2024, 16, 383. https://doi.org/10.3390/pharmaceutics16030383
Galimberti S, Abruzzese E, Luci G, Baratè C, Luciano L, Iurlo A, Caocci G, Morganti R, Stefanelli F, Di Paolo A. A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia. Pharmaceutics. 2024; 16(3):383. https://doi.org/10.3390/pharmaceutics16030383
Chicago/Turabian StyleGalimberti, Sara, Elisabetta Abruzzese, Giacomo Luci, Claudia Baratè, Luigia Luciano, Alessandra Iurlo, Giovanni Caocci, Riccardo Morganti, Fabio Stefanelli, and Antonello Di Paolo. 2024. "A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia" Pharmaceutics 16, no. 3: 383. https://doi.org/10.3390/pharmaceutics16030383
APA StyleGalimberti, S., Abruzzese, E., Luci, G., Baratè, C., Luciano, L., Iurlo, A., Caocci, G., Morganti, R., Stefanelli, F., & Di Paolo, A. (2024). A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia. Pharmaceutics, 16(3), 383. https://doi.org/10.3390/pharmaceutics16030383