Trial reportBlood2016
Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients.
Trial report in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 105 citations in OpenAlex.
- Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial.Journal of hematology & oncology · 2022Trial
- Trial
- Trial
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- Innovative rapid screening for complex BCR-ABL1 kinase domain mutations in TKI-treated leukaemia patients.British journal of cancer · 2025Article
- Synergistic effect of asciminib with reduced doses of ponatinib in human Ph + myeloid leukemia with the T315M mutation.International journal of hematology · 2025Article
- Overcoming clinical BCR-ABL1 compound mutant resistance with combined ponatinib and asciminib therapy.Cancer cell · 2024Article
- Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.MedComm · 2024Review
- Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis.Orphanet journal of rare diseases · 2024Article
- Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia.International journal of biological sciences · 2024Review
- Resistance mutations in CML and how we approach them.Hematology. American Society of Hematology. Education Program · 2023Review
- European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia.Leukemia · 2023Review
- Long non-coding RNAs regulate treatment outcome in leukemia: What have we learnt recently?Cancer medicine · 2023Review
- Asciminib: the first-in-class allosteric inhibitor of BCR::ABL1 kinase.Blood research · 2023Review
- A customized mass array panel forJournal of mass spectrometry and advances in the clinical lab · 2023Article
- B-cell receptor repertoire sequencing: Deeper digging into the mechanisms and clinical aspects of immune-mediated diseases.iScience · 2022Review
- Impact of metformin on tyrosine kinase inhibitor response in chronic myeloid leukemia.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2022Observational
- Population Pharmacokinetics of Ponatinib in Healthy Adult Volunteers and Patients With Hematologic Malignancies and Model-Informed Dose Selection for Pediatric Development.Journal of clinical pharmacology · 2022Article
- A review of the therapeutic role of the new third-generation TKI olverembatinib in chronic myeloid leukemia.Frontiers in oncology · 2022Review
- Article
Corrections and comments
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Authors and funding
21 authors at 15 institutions in 6 countries.
Funding
Abstract
BCR-ABL1 kinase domain mutations can confer resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In preclinical studies, clinically achievable concentrations of the third-generation BCR-ABL1 TKI ponatinib inhibit T315I and all other single BCR-ABL1 mutants except T315M, which generates a single amino acid exchange, but requires 2 sequential nucleotide exchanges. In addition, certain compound mutants (containing ≥2 mutations in cis) confer resistance. Initial analyses based largely on conventional Sanger sequencing (SS) have suggested that the preclinical relationship between BCR-ABL1 mutation status and ponatinib efficacy is generally recapitulated in patients receiving therapy. Thus far, however, such analyses have been limited by the inability of SS to definitively identify compound mutations or mutations representing less than ~20% of total alleles (referred to as "low-level mutations"), as well as limited patient follow-up. Here we used next-generation sequencing (NGS) to define the baseline BCR-ABL1 mutation status of 267 heavily pretreated chronic phase (CP)-CML patients from the PACE trial, and used SS to identify clonally dominant mutants that may have developed on ponatinib therapy (30.1 months median follow-up). Durable cytogenetic and molecular responses were observed irrespective of baseline mutation status and included patients with compound mutations. No single or compound mutation was identified that consistently conferred primary and/or secondary resistance to ponatinib in CP-CML patients. Ponatinib is effective in CP-CML irrespective of baseline mutation status.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.