Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the <scp>S</scp>panish compassionate use program

García‐Gutiérrez, Valentín; Martínez‐Trillos, Alejandra; Lorenzo, José Luis López; Bautista, Guiomar; Mateos, María Luisa Martin; Alvarez‐Larrán, Alberto; Pérez, Ana Iglesias; Collado, Andrés Romo; Fernández, Ana; Portero, Angeles; Cuevas, Beatriz; Ruíz, Concepción; Romero, Esperanza; Ortega, Fernando; Mata, Isabel; Tallón, J Ríos; Garay, Maria del Carmen García; Sánchez, María José Ramirez; Heras, Natalia de las; Giraldo, Pilar; Bobillo, Sabela; Castro, José María Guinea de; Debén, Guillermo; Valencia, Sandra Villacís; Sebrango, Ana; Boqué, Concepción; Maestro, Beatríz; Steegmann, Juan Luis

doi:10.1002/ajh.23973

Cited by 21 publications

(19 citation statements)

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“…Eleven articles were excluded on the basis of the prespecified eligibility criteria and authors’ combined assessment of relevance (five pharmacokinetic studies in healthy volunteers [ 21–25 ], three studies in newly diagnosed patients [ 6 , 10 , 26 ], one retrospective analysis of fourth-line bosutinib as part of a compassionate use program [ 27 ], one study in patients with advanced leukemias [ 8 ], and one article summarizing the EU conditional marketing authorization for bosutinib [ 12 ]).…”

Section: Resultsmentioning

confidence: 99%

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

2018

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Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strategies for managing these toxicities. As bosutinib is not currently indicated for newly diagnosed CML, toxicities associated with first-line treatment are not reviewed. Recognition and optimal management of these toxicities can facilitate patient compliance and affect treatment outcomes.

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Section: Resultsmentioning

confidence: 99%

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

2018

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“…The choice in 3rd line can be from among nilotinib, dasatinib, bosutinib and ponatinib rather than stipulating the order that they must be used. Bosutinib could be an option for the CML situations which preclude the use of other TKIs 14. In a Spanish study, cross intolerance with bosutinib was extremely rare, of the 7 patients who had rash with imatinib, only 1 suffered rash with bosutinib.…”

Section: Difficulties In the Treatment Of CML After Multi-tki Failurementioning

confidence: 99%

Drug Therapy in the Progressed CML Patient With Multi-Tki Failure

Haznedaroğlu

2015

Mediterr J Hematol Infect Dis

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The aim of this paper is to outline pharmacotherapy of the ‘third-line management of CML’ (progressive disease course after sequential TKI drugs). Current management of CML with multi-TKI failure is reviewed. TKI (bosutinib, ponatinib, dasatinib, nilotinib) and non-TKI (omacetaxine mepussecinate, IFN or PEG-IFN) drugs are available. The literature search was made in PubMed with particular focus on the clinical trials, recommendations, guidelines and expert opinions, as well as international recommendations. Progressing CML disease with multi-TKI failure should be treated with alloSCT based on the availability of the donor and EBMT transplant risk scores. The TKI and non-TKI drugs shall be used to get best promising (hematological, cytogenetic, molecular) response. During the CP-CML phase of multi-TKI failure, 2nd generation TKIs (nilotinib or dasatinib) should be tried if not previously utilized. Bosutinib and ponatinib (3rd-generation TKIs) should be administered in double- or triple-TKI (imatinib and nilotinib and dasatinib) resistant patients. The presence of T315I mutation at any phase requires ponatinib or omacetaxine mepussecinate therapy before allografting. During the AP/BC-CML phase of multi-TKI failure, the most powerful TKI available (ponatinib or dasatinib if not previously used) together with chemotherapy should be given before alloSCT. Monitoring of CML disease and drug off-target risks (particularly vascular thrombotic events) are vital.

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“…Importantly, the probability of crossintolerance across different TKIs is generally low. [20][21][22] This is particularly true for nonhematologic adverse events which occur infrequently, particularly at a grade 3 or 4 level, and rarely lead to treatment discontinuation for the same adverse event. In contrast, hematologic adverse events, particularly thrombocytopenia, are more likely to lead to cross-intolerance.…”

Section: Sequencing and Safetymentioning

confidence: 99%

Chronic myeloid leukemia: sequencing of TKI therapies

Cortes

Kantarjian

2016

Hematology

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Multiple tyrosine kinase inhibitors (TKIs) are available for managing patients with chronic myeloid leukemia. Although most patients have a favorable outcome with their initial therapy, whether imatinib or a second-generation TKI was used, some will require subsequent use of one or more different TKIs. Such sequencing might be indicated in a reactive way (ie, for patients who have experienced resistance or intolerance to their initial therapy) or in a proactive way (ie, for patients with a somewhat favorable outcome who have not reached an "optimal" outcome). Sequencing of TKIs has become standard practice, and the proper use of sequenced TKIs is likely to optimize outcomes and resource utilization. Learning Objectives• Assess the different scenarios in which TKI sequencing can be used in patients with chronic myeloid leukemia • Critically review the outcomes associated with sequencing of TKI in patients with chronic myeloid leukemia Tyrosine kinase inhibitors (TKIs) became standard therapy for patients with chronic myeloid leukemia (CML) not long after the first patient received STI571 (later known as imatinib mesylate) on a phase I clinical trial. 1 The initial approved indication was for patients with resistance to or intolerance of interferon alpha-based therapy, the standard at the time. By 2003, imatinib was approved as frontline therapy for CML, 2 and since then, nearly all patients with access to TKIs have received them as initial therapy. Shortly thereafter, secondgeneration agents, including dasatinib, nilotinib, and bosutinib, with increased potency, different structures that allowed them to overcome most mutations leading to resistance to TKIs, and different toxicity profiles, were introduced and eventually received regulatory approval. Later, ponatinib, a drug with activity against T315I and all mutations tested, proved effective in overcoming resistance in most patients, even those who had received 3 or more prior TKIs. All TKIs were eventually compared with imatinib in the first-line setting, and they generally demonstrated higher response rates, with deeper and faster responses which, in the case of dasatinib and nilotinib, were sufficient to lead to their approval as initial therapy for patients with chronic phase CML (CML-CP). This rapid development has resulted in the availability of multiple TKIs, and along with this, the sequential use of various TKIs in patients with CML-CP (Figure 1).The use of sequential TKI therapy, regardless of the choice of initial therapy, is perhaps more common than is usually appreciated. Despite the professed efficacy of initial therapy with TKIs, at least onethird of all patients initially treated in clinical trials with any TKI for newly diagnosed CML, whether imatinib or a second-generation TKI, have received at least one additional TKI. After 5 years of follow-up in the DASISION trial (in the final report), 39% of patients initially treated with dasatinib and 37% of those treated with imatinib are no longer receiving their initial therapy.3 Similarly, the 5-ye...

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Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the Spanish compassionate use program

Cited by 21 publications

References 15 publications

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

Drug Therapy in the Progressed CML Patient With Multi-Tki Failure

Chronic myeloid leukemia: sequencing of TKI therapies

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