The Real World Use of Bosutinib in Patients with Chronic Myeloid Leukaemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5435-5435
Author(s):  
Jane F. Apperley ◽  
Jenny L. Byrne ◽  
Graeme Smith ◽  
Simone Claudiani ◽  
Andrea Viqueira ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Data Collection ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Real World ◽  
Molecular Response ◽  
Major Molecular Response ◽  
The Real ◽  
Advisory Boards ◽  
Grade 3

Abstract Objectives.Bosutinib is a second-generation tyrosine kinase inhibitor (TKI) indicated for patients with previously treated Philadelphia chromosome positive chronic myeloid leukaemia (CML) when imatinib, nilotinib and dasatinib are not appropriate. Data describing the use of bosutinib in patients with CML in the real world clinical setting are limited. The objective of this study was to describe the efficacy and safety of bosutinib in patients with CML used under routine clinical practice. Methods.An international, multi-centre, retrospective, non-interventional study in hospitals in the UK (n=7) and the Netherlands (n=2). Fifty-three patients (32 [60%] male) with CML, aged ≥18 years at bosutinib initiation and with ≥3 months data available post-initiation were recruited. Surviving patients provided written informed consent for data collection; data from deceased patients were collected by a member of the direct care team to preserve confidentiality. Data were analysed using descriptive statistics with no imputation of missing values (denominators presented where data are missing). Results.Median age at bosutinib initiation was 63.6 (range: 25.5 to 90.1) years; median time from CML diagnosis to bosutinib initiation was 7.1 (range: 0.5 to 35.7) years; 74% (39/53) of patients had one or more co-morbidities at initiation. Bosutinib was 3rd-line TKI in 32% (17/53) of patients and 4th-line TKI in 53% (28/53) of patients. Fifty-seven percent (30/53) of patients switched to bosutinib due to intolerance and 26% (14/53) due to resistance to a previous TKI. The most common bosutinib starting dose was 300 mg/day (28% [15/53] of patients). Median bosutinib treatment duration was 15.6 (range: 0.4 to 66.0) months. The proportions of patients with cumulative complete cytogenetic response (CCyR), major molecular response (MMR), molecular response 4.0 (MR4.0) and molecular response 4.5 (MR4.5) with bosutinib were 62%, 54%, 34% and 26%, respectively (see figure). At data collection (median follow-up 25.1 [range: 3.0 to 66.0] months), 38% (20/53) of patients had discontinued bosutinib; 2% (1/53) discontinued due to progression, 8% (4/53) due to treatment failure, 15% (8/53) due to adverse events (AE), 6% (3/53) due to loss of response, and 4% (2/53) due to patient request. Ninety-two percent (49/53) of patients experienced ≥1 AE, most commonly diarrhoea (55% [29/53] of patients); 26% (14/53) of patients had grade 3/4 AEs (diarrhoea grade 3/4: 4% [2/53] of patients). Conclusions.Bosutinib used in normal clinical practice in pre-treated patients with CML demonstrates high rates of cytogenetic and major molecular response similar to those seen in clinical trials. Bosutinib is generally well tolerated, with the majority of patients not experiencing grade 3/4 AEs, despite most patients having pre-existing co-morbidities. Disclosures Apperley: Pfizer: Honoraria, Speakers Bureau; Ariad: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Byrne:Bristol Myers Squipp: Consultancy, Speakers Bureau. Smith:Pfizer: Honoraria, Other: Advisory boards and talks at regional sponsored meetings. Viqueira:Pfizer: Employment. Ferdinand:Pfizer: Employment. Carter:pH Associates: Employment. Nock:pH Associates: Employment. Milojkovic:Ariad: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.

scholarly journals PF-114: A 4th Generation Tyrosine Kinase-Inhibitor for Chronic Phase Chronic Myeloid Leukaemia Including BCRABL1T315I

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1638-1638 ◽  
Author(s):  
Anna G. Turkina ◽  
Olga Vinogradova ◽  
Elza Lomaia ◽  
Evgeniya Shatokhina ◽  
Oleg A. Shukhov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Myeloid Leukaemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukaemia ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Molecular Response ◽  
Travel Grant ◽  
Grade 3

Background: PF-114 is a 4th-generation oral tyrosine kinase-inhibitor (TKI) active against wild-type and mutated BCR-ABL1 isoforms including BCR-ABL1T315I. We present data from a phase-1 study in patients with chronic or accelerated phase chronic myeloid leukaemia (CML) failing ≥2 TKIs or with BCR-ABL1T315I (NCT02885766) with ≥6 months therapy. Methods: 3+3 dose-escalation study to determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary objectives included safety and efficacy based on haematological, cytogenetic, and molecular criteria. Adverse events (AEs) were graded using NCI-CTCAE v4.03. Results: 51 patients were enrolled. Daily doses were 50 mg (n=3), 100 mg (n=3), 200 mg (n=9), 300 mg (n=11), 400 mg (n=12), 500 mg (n=3), 600 mg (n=6), 750 mg (n=4) given continuously. Median age was 50 years (range, 29-82 years). Median CML duration pre-study was 10 years (range, 0.3-23 years). All patients had baseline ECOG performance scores 0-1. Twelve patients had BCR-ABL1T315I. Patients were heavily pre-treated: 25 received ≥3 prior TKIs; 5 patients with BCR-ABL1T315I received 1 prior TKI. Interim analysis was conducted at follow-up of ≥6 months (cut-off date January 16th 2019). Therapy was ongoing in 17 patients at doses 200 mg (n=4), 300 mg (n=9), 400 mg (n=3) and 600 mg (n=1) with median duration of exposure of 7,4 (range, 4,6-26), 9,2 (range, 7,4-26), 9,2 (range, 8,3-9,2) and 9,2 months. Other patients discontinued because of progression (n=18), adverse events (n=6), consent withdrawal (n=4), participation in another study (n=3) or other reasons (n=3). The MTD was 600 mg with the grade-3 psoriasis-like skin lesions the DLT, which occurred during the first 28 days of treatment. Reversible grade-3 skin toxicity occurred in 11 patients at doses ≥400 mg. There were no other drug-related non-hematologic grade-3 toxicities except 1 grade-3 toxic hepatitis at 400 mg and there were no detectable effects on ankle-brachial index or vascular occlusive events. The best safety/efficacy dose was 300 mg/d with 6 of 11 patients achieving a major cytogenetic response (MCyR) and 4 of them - a major molecular response (MMR). Higher doses were less effective probably because of toxicity-related therapy interruptions and discontinuations. Five of 12 patients with BCR-ABL1T315I responded, 3 of which achieved a complete hematologic response and 4 achieved MCyR. Conclusion: PF-114 was safe and effective in patients with CML failing ≥2 TKIs or with BCR-ABL1T315I. The most effective dose was 300 mg/d. Five of 12 patients with BCR-ABL1T315I responded. A pivotal study is beginning. Disclosures Turkina: Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; fusion pharma: Consultancy; Novartis: Consultancy, Speakers Bureau. Vinogradova:Novartis: Consultancy; Fusion Pharma: Consultancy. Lomaia:Novartis: Other: Travel Grant;Lecture fee; Pfizer: Other: Travel Grant. Shukhov:Pfizer: Consultancy; Novartis: Consultancy. Chelysheva:Novartis: Consultancy, Honoraria; Fusion Pharma: Consultancy. Shikhbabaeva:Novartis: Consultancy; Fusion Pharma: Consultancy. Shuvaev:Fusion Pharma: Consultancy; Novartis: Consultancy; Pfize: Honoraria; BMS: Consultancy. Cortes:Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; BiolineRx: Consultancy; Sun Pharma: Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding. Baccarani:Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Takeda: Consultancy. Ottmann:Roche: Honoraria; Pfizer: Honoraria; Fusion Pharma: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Mikhailov:Fusion Pharma: Employment. Novikov:Fusion Pharma: Employment. Shulgina:Fusion Pharma: Employment. Chilov:Fusion Pharma: Consultancy.

Imatinib plasma levels in patients with chronic myeloid leukaemia under routine clinical practice conditions

2021 ◽  
pp. 107815522110525
Author(s):  
Betel Del Rosario García ◽  
Iris González García ◽  
María Micaela Viña Romero ◽  
Jonathan González García ◽  
Ruth Ramos Díaz ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Therapeutic Range ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Routine Clinical Practice ◽  
Daily Routine ◽  
Molecular Response ◽  
Therapeutic Success

Introduction The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety. In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. Methods We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019–2020 were analysed. An optimal therapeutic range of 750–1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). Results A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response ( p = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL ( p = 0.039). Conclusions This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

scholarly journals Nilotinib therapy after resistance and intolerance to imatinib in CML patient with trisomy of the chromosome 8

2015 ◽  
Vol 4 (5S) ◽  
pp. 23-27
Author(s):  
Antonella Russo Rossi
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Chromosome 8 ◽  
Molecular Response ◽  
Second Line ◽  
Major Molecular Response ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
Genetic Anomaly ◽  
Complete Molecular Response

In this article is presented the case of a 30-year-old woman with chronic myeloid leukaemia (CML) treated with imatinib for 15 months, and then with nilotinib as second-line therapy. Two episodes of grade 3 neutropenia, the detection of the trisomy of chromosome 8 and the failed achievement of a major molecular response (MMolR) in 15 months led to the switch to nilotinib. With nilotinib the patient obtained the lack of the genetic anomaly in 3 months and a complete molecular response (CMolR) in 6 months, all confirmed at 9 months. No haematologic or extra-haematologic adverse events were detected with this second-line agent.

scholarly journals Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

2017 ◽  
Vol 28 ◽  
pp. iv41-iv51 ◽  
Author(s):  
A. Hochhaus ◽  
S. Saussele ◽  
G. Rosti ◽  
F.-X. Mahon ◽  
J.J.W.M. Janssen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines

scholarly journals Treatment-Free Remission in Chronic Myeloid Leukaemia: Can We Identify Prognostic Factors?

2021 ◽  
Author(s):  
Hilbeen Hisham Saifullah ◽  
Claire Marie Lucas
Keyword(s):  
Prognostic Factors ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Response ◽  
Predicting Success ◽  
Treatment Free Remission ◽  
Almost All ◽  
Tki Discontinuation

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

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