Real-life comparison of nilotinib versus dasatinib as second-line therapy in chronic phase chronic myeloid leukemia patients

Scalzulli, Emilia; Caocci, Giovanni; Efficace, Fabio; Rizzo, Lorenzo; Colafigli, Gioia; Prima, Alessio Di; Pepe, Sara; Fegatelli, Danilo Alunni; Carmosino, Ida; Diverio, Daniela; Latagliata, Roberto; Nasa, Giorgio La; Martelli, Maurizio; Foà, Robin; Breccia, Massimo

doi:10.1007/s00277-021-04477-0

Cited by 5 publications

(2 citation statements)

References 24 publications

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“…Use of 2G-TKIs is associated with lower rates of resistance than imatinib, but still relevant: the reason for the switch after a frontline 2G-TKI, in clinical trial or real-life setting is treatment failure in about 10–40% of cases [ 15 , 161 , 162 , 163 , 164 , 165 , 166 ]. Prior failure is associated with a higher risk of a subsequent failure, with resistance rates increasing up to 50–65% in the second-line setting [ 160 , 167 , 168 ]. The molecular milestones to second-line treatment are the same as to first-line treatment [ 18 ], and, as for patients on frontline therapy, initial molecular response at 3 and 6 months on second-line therapy has predictive value [ 169 , 170 , 171 , 172 ].…”

Section: Prognostic Factors Beyond the Baselinementioning

confidence: 99%

Prognosis in Chronic Myeloid Leukemia: Baseline Factors, Dynamic Risk Assessment and Novel Insights

Iezza

Cortesi

Ottaviani

et al. 2023

Cells

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The introduction of tyrosine kinase inhibitors (TKIs) has changed the treatment paradigm of chronic myeloid leukemia (CML), leading to a dramatic improvement of the outcome of CML patients, who now have a nearly normal life expectancy and, in some selected cases, the possibility of aiming for the more ambitious goal of treatment-free remission (TFR). However, the minority of patients who fail treatment and progress from chronic phase (CP) to accelerated phase (AP) and blast phase (BP) still have a relatively poor prognosis. The identification of predictive elements enabling a prompt recognition of patients at higher risk of progression still remains among the priorities in the field of CML management. Currently, the baseline risk is assessed using simple clinical and hematologic parameters, other than evaluating the presence of additional chromosomal abnormalities (ACAs), especially those at “high-risk”. Beyond the onset, a re-evaluation of the risk status is mandatory, monitoring the response to TKI treatment. Moreover, novel critical insights are emerging into the role of genomic factors, present at diagnosis or evolving on therapy. This review presents the current knowledge regarding prognostic factors in CML and their potential role for an improved risk classification and a subsequent enhancement of therapeutic decisions and disease management.

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Section: Prognostic Factors Beyond the Baselinementioning

confidence: 99%

Prognosis in Chronic Myeloid Leukemia: Baseline Factors, Dynamic Risk Assessment and Novel Insights

Iezza

Cortesi

Ottaviani

et al. 2023

Cells

View full text Add to dashboard Cite

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“…In addition, data concerning the frequency of deep molecular response (DMR: MR 4.0 and MR 4.5 ) after a 2-line treatment with 2G-TKI is unsatisfactory. A real-life comparison of nilotinib versus dasatinib as second-line therapy in CML-CP patients with IM therapy failure showed that only 47% and 38% of 108 evaluable patients achieved an major molecular response (MMR) BCR::ABL1 [on the International Scale (IS) <0.1%], and 18.2% and 16.2% a DMR, with dasatinib and nilotinib, respectively, after 12 months of treatment [12].…”

Section: Introductionmentioning

confidence: 99%

Asciminib a new player in treatment of TKI-resistant/intolerant chronic phase chronic myelogenous leukemia

Lewandowski

2024

Acta Haematol Pol.

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The introduction in 1998 of imatinib mesylate (IM), a first-generation BCR-ABL1 tyrosine kinase inhibitor (1G-TKI), to the treatment of chronic myelogenous leukemia patients in the chronic phase (CML-CP), significantly improved the prognosis of a previously incurable disease with a prognosed 5-year-long overall survival and progression-free survival of 91.7% and 94.7%, respectively. Long term follow-up studies of CML-CP patients verified the initial results, showing a 10-year overall response rate of 82-83.2%. In about one quarter of CML-CP patients, IM primary/secondary resistance or intolerance is diagnosed. After switching to a second generation BCR-ABL1 TKI (dasatinib, nilotinib, bosutinib), a complete cytogenetic response is obtained in only c. 50% of CML-CP patients. Also the frequency of deep molecular responses (DMR: MR 4.0 and MR 4.5 ) is relatively low. The results of 2G-TKI treatment are particularly unsatisfactory in patients carrying the TKI resistant BCR::ABL1 kinase domain mutants (BCR::ABL1 KD), especially BCR-ABL1 T315I. For this reason, other orally biocompatible compounds have been developed to target BCR-ABL T315I. One of these is ponatinib, which allows a major molecular response (MMR) and MR 4.5 to be obtained in 40% and 24% of severely TKIs-pretreated CML-CP patients, respectively. The latter represent a new class of allosteric BCR-ABL1 tyrosine kinase inhibitor [asciminib (ABL001)], specifically targeting the ABL myristoyl pocket of BCR-ABL tyrosine kinase. Its application in CML-CP patients previously treated with at least two TKIs resulted in an MMR rate and a MR 4.5 rate of 37.6% and 10.8%, respectively, at 96 weeks. The favorable asciminib response and tolerance profile was also confirmed in real--life conditions, even in subjects with previous ponatinib therapy failure (MR 4.5 in 10.5%). Recent data suggests that asciminib may be used in the first line or in combination with a 1G-or 2G-TKI. This latter strategy may enhance the rate of DMR obtained and increase the number of patients eligible for an attempt at treatment-free remission.

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Investigation on the interaction behavior of afatinib, dasatinib, and imatinib docked to the BCR-ABL protein

2021

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Real-life comparison of nilotinib versus dasatinib as second-line therapy in chronic phase chronic myeloid leukemia patients

Cited by 5 publications

References 24 publications

Prognosis in Chronic Myeloid Leukemia: Baseline Factors, Dynamic Risk Assessment and Novel Insights

Prognosis in Chronic Myeloid Leukemia: Baseline Factors, Dynamic Risk Assessment and Novel Insights

Asciminib a new player in treatment of TKI-resistant/intolerant chronic phase chronic myelogenous leukemia

Investigation on the interaction behavior of afatinib, dasatinib, and imatinib docked to the BCR-ABL protein

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