Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1/2 trial

Copland, Mhairi; Slade, Daniel; McIlroy, Graham; Horne, Gillian A.; Byrne, Jenny; Rothwell, Kate; Brock, Kristian; Lavallade, Hugues de; Craddock, Charles; Clark, Richard E.; Smith, Matthew; Fletcher, Rachel; Bishop, R. F.; Milojković, Dragana; Yap, Christina

doi:10.1016/s2352-3026(21)00370-7

Cited by 25 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Copland and colleagues reported the early results of FLAG‐IDA and ponatinib at a starting dose of 30 mg in 17 evaluable patients in blast phase CML 157 . Clinical responses were observed in 11/17 patients (65%); five achieved MMR.…”

Section: Advanced Stage CMLmentioning

confidence: 99%

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

2022

View full text Add to dashboard Cite

Disease Overview Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. Diagnosis CML is characterized by a balanced genetic translocation, t (9;22) (q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. Frontline Therapy Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib are approved by the United States Food and Drug Administration for first‐line treatment of newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. Salvage Therapy For CML post failure on frontline therapy, second‐line options include second and third generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML‐CP and failure (due to resistance) of at least two TKIs, and for all patients in advanced phase disease. Older patients who have a cytogenetic relapse post failure on all TKIs can maintain long‐term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non‐TKI anti‐CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, busulfan and others).

show abstract

Section: Advanced Stage CMLmentioning

confidence: 99%

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

2022

View full text Add to dashboard Cite

show abstract

“…Within the recent MATCHPOINT clinical trial for UK patients with BP-CML, the ELN definition of 30% or more blasts was used as an entry criterion. 10 Extramedullary blast proliferation is also diagnostic of BP-CML, regardless of disease phase in the bone marrow. 7,8 Where a diagnosis of BP-CML is suspected, a bone marrow aspirate should be performed to evaluate morphology, immunophenotyping to confirm if myeloid, lymphoid or mixed phenotype, and full karyotype to identify any additional cytogenetic abnormalities (ACAs).…”

Section: Agnosis Of Bl Ast Ph Ase Chron Ic M Y E Loid L Eu K a E M I Amentioning

confidence: 99%

“…Overall survival (OS) was significantly better in patients with 20%–29% blasts as compared to those with blasts at 30% or more with three‐year OS of 42% versus 10%, respectively. Within the recent MATCHPOINT clinical trial for UK patients with BP‐CML, the ELN definition of 30% or more blasts was used as an entry criterion 10 . Extramedullary blast proliferation is also diagnostic of BP‐CML, regardless of disease phase in the bone marrow 7,8 …”

Section: Diagnosis Of Blast Phase Chronic Myeloid Leukaemiamentioning

confidence: 99%

“…Within the UK, we have recently published the Phase 1/2 MATCHPOINT clinical trial, using an Eff‐Tox design, combining ponatinib with the chemotherapy regimen FLAG‐IDA (fludarabine, cytarabine, idarubicin and granulocyte‐colony stimulating factor [G‐CSF]) 10 . Patients received either one or two cycles of FLAG‐IDA with ponatinib 30 mg daily, and then proceeded to alloHSCT.…”

Section: Combination Therapiesmentioning

confidence: 99%

“…An ongoing Phase 2 study (PONAZA; http://www.clinicaltrials.gov NCT03895671; accessed 8th April 2022) aims to recruit up to 40 patients with AP‐ or BP‐CML and assess the combination of ponatinib at a starting dose of 45 mg daily with azacytidine. It will be interesting to compare the results of this study with MATCHPOINT to better understand the optimal approach to treating myeloid BP‐CML 10 …”

Section: Combination Therapiesmentioning

confidence: 99%

See 2 more Smart Citations

Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity

Copland

2022

Br J Haematol

Self Cite

View full text Add to dashboard Cite

Chronic myeloid leukaemia (CML) is a relatively rare form of myeloproliferative neoplasm, with an incidence of 0.7-1.0/100 000. 1 CML has the hallmark genetic lesion the Philadelphia (Ph) chromosome, a reciprocal translocation between the long arms of chromosomes 9 and 22, with the resultant shortened chromosome 22 being the aforementioned Ph chromosome, producing the oncogenic fusion protein BCR-ABL1, a constitutively active tyrosine kinase. 2 CML is a triphasic disorder. The majority of patients present in chronic phase (CP), associated with a raised white cell

show abstract

Chronic Myeloid Leukemia: Advance Phases of the Disease

Mauro

2023

Cancer Consult

View full text Add to dashboard Cite

Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1/2 trial

Cited by 25 publications

References 37 publications

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity

Chronic Myeloid Leukemia: Advance Phases of the Disease

Contact Info

Product

Resources

About