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Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML.

ABSTRACT: Within the International Registry of Childhood Chronic Myeloid Leukemia (CML), we identified 18 patients less than 18 years old at diagnosis of CML who were in the chronic phase and exhibiting a sustained deep molecular response (DMR) to imatinib defined as BCR-ABL1/ABL1 < 0.01% (MR⁴) for at least two years followed by discontinuation of imatinib. Before discontinuation, the median duration of imatinib was 73.2 months (range, 32-109) and the median duration of MR⁴ was 46.2 months (range, 23.9-98.6). Seven patients experienced loss of major molecular response (MMR) 4.1 months (range, 1.9-6.4) after stopping and so restarted imatinib. The median molecular follow-up after discontinuation was 51 months (range, 6-100) for the nine patients without molecular relapse. The molecular free remission rate was 61% (95% CI, 38-83%), 56% (95% CI, 33-79%) and 56% (95% CI, 33-79%) at 6, 12 and 36 months, respectively. Six of the seven children who experienced molecular relapse after discontinuation regained DMR (median, 4.7 months; range, 2.5-18) after restarting imatinib. No withdrawal syndrome was observed. In univariate analysis, age, sex, Sokal and ELTS scores, imatinib treatment and DMR durations before discontinuation had no influence on treatment free remission. These data suggest that imatinib can be safely discontinued in children with sustained MR⁴ for at least two years.

SUBMITTER: Millot F

PROVIDER: S-EPMC8392145 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:Cytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association be- tween single nucleotide polymorphisms (SNPs) in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM) affecting clinico-pathological parameters, in the Indian population. MATERIALS AND METHODS:In this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genom- ic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2C polymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters. RESULTS:We observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs. 16%, P=0.0001), AG (57 vs. 78%, P=0.0002) and GG (5 vs. 6%, P=0.6635) between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs AG in major (33 vs 67%) and poor (62 vs 31%) hematological responders, and AA vs AG in major (34 vs. 65%) and poor (78 vs. 22%) cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome. CONCLUSION:The higher frequency of AG in controls indicates that AG may play a protec- tive role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards imatinib therapy, indicating that this polymorphism could serve as a good therapeutic marker in predicting response to such therapy.

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Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML.

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