ORCID Profile
0000-0002-4508-0353
Current Organisation
University of Bologna
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Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-2009
Abstract: Nilotinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase (CP CML-CP) and accelerated phase (AP CML-AP) who are resistant to or intolerant of prior imatinib therapy. In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed. Baseline mutation data were assessed in 281 (88%) of 321 patients with CML-CP in the phase II nilotinib registration trial. Among imatinib-resistant patients, the frequency of mutations at baseline was 55%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 40%, and major molecular response (MMR) in 29% of patients without baseline mutations versus 49% (P = .145), 32% (P = .285), and 22% (P = .366), respectively, of patients with mutations. Responses in patients who harbored mutations with high in vitro sensitivity to nilotinib (50% inhibitory concentration [IC 50 ] ≤ 150 nM) or mutations with unknown nilotinib sensitivity were equivalent to those responses for patients without mutations (not significant). Patients with mutations that were less sensitive to nilotinib in vitro (IC 50 150 nM Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR none achieved CCyR. For most patients with imatinib resistance and with mutations, nilotinib offers a substantial probability of response. However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib.
Publisher: Springer Science and Business Media LLC
Date: 11-2008
DOI: 10.1038/LEU.2008.231
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.LEUKRES.2013.09.011
Abstract: Patients with chronic myeloid leukemia develop resistance to both first-generation and second-generation tyrosine kinase inhibitors (TKIs) as a result of mutations in the kinase domain (KD) of BCR-ABL1. A wide range of BCR-ABL1 KD mutations that confer resistance to TKIs have been identified, and the T315I mutant has proven particularly difficult to target. This review summarizes the prevalence, impact, and prognostic implications of BCR-ABL1 KD mutations in patients with chronic myeloid leukemia who are treated with current TKIs and provides an overview of recent treatment guidelines and future trends for the detection of mutations.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 15-05-2023
Publisher: American Society of Hematology
Date: 08-08-2013
DOI: 10.1182/BLOOD-2013-05-501569
Abstract: Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, % at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas % at 6 months and % from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome–positive [Ph+] %) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2013
Publisher: Public Library of Science (PLoS)
Date: 25-07-2012
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-12-2012
Abstract: The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of 0.1% to ≤ 1%, 1% to ≤ 10%, and 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR–ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of 10%. Patients with BCR-ABL1 (IS) of 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 08-08-2013
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2018
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2018
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 29-12-2012
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 06-2020
No related grants have been discovered for SIMONA SOVERINI.