Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors

Lipton, Jeff H.; Bryden, Peter; Sidhu, M.; Huang, Hui; McGarry, Lisa; Lustgarten, Stephanie; Mealing, Stuart; Woods, Beth; Whelan, Jo; Hawkins, Neil

doi:10.1016/j.leukres.2014.10.005

Cited by 48 publications

(38 citation statements)

References 23 publications

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“…Considering the extent of prior exposure to multiple TKIs in this patient population, these results compare favorably with those of second-generation TKIs in both the second-line setting and later lines. 8,[12][13][14][15][16][17][18] In studies of CP-CML patients who received their second TKI after resistance or intolerance to imatinib only: 57% achieved MCyR while receiving dasatinib (100 mg once daily), with 87% of these patients maintaining MCyR at 2 years 13 ; 51% achieved MCyR while receiving nilotinib, with 62% of these patients having MCyR lasting .18 months 16 ; and 59% achieved or maintained baseline MCyR while receiving bosutinib, with a 77% probability of maintaining MCyR at 2 years. 17 In the only other prospective evaluation of a TKI for patients treated with 2 or (rarely) 3 prior TKIs, 32% of CP-CML patients achieved MCyR with bosutinib, and the probability of maintaining MCyR at 2 years was 59%.…”

Section: Discussionmentioning

confidence: 99%

Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: final 5-year results of the phase 2 PACE trial

Cortes

Kim

Pinilla‐Ibarz

et al. 2018

Blood

456

439

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Section: Discussionmentioning

confidence: 99%

Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: final 5-year results of the phase 2 PACE trial

Cortes

Kim

Pinilla‐Ibarz

et al. 2018

Blood

456

439

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“…However, there are also BCR-ABL1-independent mechanisms of TKI resistance, such as additional chromosomal abnormalities, which may play an important role. There is evidence from a comparative analysis suggesting that in CP-CML patients failing a 2G TKI, treatment responses with ponatinib are likely 2-fold higher compared to sequential 2G TKI treatment (complete cytogenetic response, CCyR: 60 vs. 22–26%) [5].…”

Section: Introductionmentioning

confidence: 99%

Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management

et al. 2019

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Treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute leukemia (Ph+ ALL) has been revolutionized with the advent of tyrosine kinase inhibitors (TKIs). Most patients with CML achieve long-term survival similar to individuals without CML due to treatment with TKIs not only in frontline but also in further lines of therapy. The third-generation TKI ponatinib has demonstrated efficacy in patients with refractory CML and Ph+ ALL. Ponatinib is currently the most potent TKI in this setting demonstrating activity against T315I mutant clones. However, ponatinib’s safety data revealed a dose-dependent, increased risk of serious cardiovascular (CV) events. Guidance is needed to evaluate the benefit–risk profile of TKIs, such as ponatinib, and safety measures to prevent treatment-associated CV events. An expert panel of German hematologists and cardiologists summarize current evidence regarding ponatinib’s efficacy and CV safety profile. We propose CV management strategies for patients who are candidates for ponatinib.

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“…In summary, approximately 60% of CML patients under 2G TKI treatment can develop a further event with a median interval between the first and next event of about 8 months, regardless of dose reduction . Ponatinib was superior in the third‐line setting in CP‐CML patients resistant/intolerant to ≥1 prior 2G TKIs, in terms of obtaining CCyR or MMR . The efficacy of ponatinib is not compromised by age or by reduced doses …”

Section: Ponatinib In Chronic Myeloid Leukemiamentioning

confidence: 97%

The multi‐tyrosine kinase inhibitor ponatinib for chronic myeloid leukemia: Real‐world data

Luciano

Annunziata

Attolico³

et al. 2020

European J of Haematology

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Development of the highly selective targeted tyrosine kinase inhibitors (TKIs) has expanded the therapeutic options for chronic myeloid leukemia (CML). Patients undergoing TKI therapy should be closely monitored to ensure that the best therapeutic response and quality of life are achieved, and to control suboptimal responses and adverse events. Despite the high rate of response using current first‐line TKIs, treatment failure may still occur, and resistance is considered a challenge in the treatment of patients with CML. The third‐generation TKI, ponatinib, is a potent orally bioavailable pan BCR‐ABL inhibitor that inhibits both wild‐type and mutant BCR‐ABL1 kinase, including the “gatekeeper” T315I mutation, which is resistant to all other currently available TKIs. This paper reviews the effectiveness, feasibility, and safety of ponatinib in the real‐life clinical management of CML. Potential prognostic factors in identifying patients most likely to benefit from ponatinib treatment will be discussed, and case presentations illustrating situations encountered in real‐life clinical practice are described. Ponatinib is effective in patients who have received prior TKIs in clinical studies as well as under real‐life conditions. Nevertheless, the risk/benefit balance must be evaluated for each patient, particularly considering disease state, mutational status, treatment line, intolerance/resistance to prior TKIs, age, frailty, and specific comorbidities.

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Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors

Cited by 48 publications

References 23 publications

Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: final 5-year results of the phase 2 PACE trial

Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: final 5-year results of the phase 2 PACE trial

Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management

The multi‐tyrosine kinase inhibitor ponatinib for chronic myeloid leukemia: Real‐world data

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