1,721,363 research outputs found
Shedding light on resistance to asciminib
No full textIn this issue of Blood, , Leyte-Vidal et al use cell-viability assays,
molecular simulations, and drug-binding studies to demonstrate that
BCR::ABL1 :: ABL1 N-lobe mutants, such as M244V, confer resistance to
asciminib, adding another potential mechanism of resistance to this
drug.1
Can Chronic-Phase Chronic Myeloid Leukemia Patients Achieve Optimal and Durable Responses after Two Failed TKI Treatments? Real-World Evidence Data
No full textImatinib improved the overall survival of chronic myeloid leukemia patients in low- and middle-income countries: A therapeutic goal has been reached
No full textMechanisms And Clinical Course Of Cardiovascular Toxicity Of Cancer Treatments: Bcr/Abl1 Kinase Inhibitors
No full textAtypical CML: diagnosis and treatment
No full textAtypical chronic myeloid leukemia (aCML) is included in the group of myelodysplastic/myeloproliferative neoplasms by the International Consensus Classification and has been renamed as MDS/MPN with neutrophilia by the fifth edition of World Health Organization classification. It is always characterized by morphologic identification of granulocytic dysplasia with >10% circulating immature myeloid cells, 2 distinguished features that differentiate this disease among the others. Somatic mutations may help to diagnose but are not specifically pathognomonic of the disease, with the most detected including ASXL1, SETBP1, NRAS, KRAS, SRSF2, and TET2 and with low-frequency CBL, CSF3R, JAK2, and ETNK1. The genomic landscape of aCML has been recently unravelling, revealing that SETBP1 and ETNK1 are usually not ancestral but secondary events associated with disease progression. Unfortunately, until now, no consensus on risk stratification and treatment has been developed: Mayo Clinic prognostic score identified as adverse events age >67 years, hemoglobin level <10 g/dL, and TET2 mutations. Although some possible genetic markers have been identified, allogeneic transplant remains the only curative strategy
First-line dasatinib discontinuation in chronic myeloid leukaemia: another step towards an ``operational cure{''}
No full textInterferon in chronic myeloid leukaemia: Is it useful for treatment-free remission?
No full textThe role of IFN alpha in chronic myeloid leukaemia patients who have
achieved a deep molecular response (DMR) is still unknown. The study
reported by Irani et al., which shows the prospective biological effects
of the drug in combination with a second-generation tyrosine kinase
inhibitor, pave the way for further clinical studies aimed at increasing
the rate of DMR for a possible successful discontinuation.
Commentary on: Irani et al. Immune modulation in chronic myeloid
leukaemia patients treated with nilotinib and interferon-alpha. Br J
Haematol 2023 (Online ahead of print). doi: 10.1111/bjh.18984
How to improve treatment-free remission eligibility in chronic myeloid leukaemia?
No full textThe achievement of treatment-free remission (TFR) has become a
significant clinical end-point in the management of patients with
chronic myeloid leukaemia (CML), providing an opportunity to discontinue
therapy with tyrosine kinase inhibitors (TKIs) while maintaining deep
molecular response (DMR). Early studies, such as the French STIM trial,
have demonstrated that a portion of patients can maintain DMR after
treatment cessation, with rates ranging from 40\% to 50\%, and most
relapses occurring within the first 6 months. Key prognostic factors for
successful TFR, including treatment duration, duration of DMR, risk
scores, and transcript type, have been identified. Optimal patient
selection for TFR remains a challenge, but recent research provides
insights into potential strategies to increase TFR eligibility. Evidence
suggests that early intervention switching to achieve optimal response,
treatment combinations, proactive switch in the case of absence of DMR,
dose-optimization and induction-maintenance approach can improve
molecular responses and, consequently, enhance TFR eligibility. In this
review, we report and discuss all the potential therapeutic strategies
that may enhance eligibility for a first attempt at TFR, with a
particular emphasis on potential future approaches.
Treatment-free remission (TFR) is pivotal in chronic myeloid leukemia
(CML) management. Patient selection remains a challenge, but
interventions like early switching to achieve optimal response,
treatment combinations, switching strategies, dose optimization and
induction-maintenance approach hold promise for improving TFR
eligibility.imag
Asciminib in chronic myeloid leukemia
No full text: Despite the fact that, in the last years, life expectancy of chronic myeloid leukemia (CML) patients has reached that of the normal population, a significant proportion of CML patients is likely to fail treatment with first- or second-generation tyrosine kinase inhibitors (TKIs). Failure to first-line treatment is commonly due to molecular resistance or unbearable toxicity. New specific compounds are tested in this setting to fulfill this unmet clinical need in CML; of these, asciminib has shown efficacy based on allosteric inhibition which allows to overcome resistance and off-target toxicity. This review aims to cover how asciminib will change the therapeutic scenario of CML, highlighting its mechanism of action, pharmacokinetics, efficacy and toxicity. Asciminib will be a possible option as third-line therapy for patients carrying resistant mutations, such as T315I, and/or not eligible for treatment with other TKIs
Prognostic Significance of Transcript-Type BCR-ABL1 in Chronic Myeloid Leukemia
No full textChronic myeloid leukemia (CML) is characterized by the presence of the
BCR-ABL1 fusion gene. In more than 95\% of CML patients, the typical
BCR-ABL1 transcript subtypes are e13a2 (b2a2), e14a2 (b3a2), or the
simultaneous expression of both. Other less frequent transcript
subtypes, such as e1a2, e2a2, e6a2, e19a2, e1a3, e13a3, and e14a3, have
been sporadically reported. The main purpose of this review is to assess
the possible impact of different transcripts on the response rate to
tyrosine kinase inhibitors (TKIs), the achievement of stable deep
molecular responses (s-DMR), the potential maintenance of treatment-free
remission (TFR), and long-term outcome of CML patients treated with
TKIs. According to the majority of published studies, patients with
e13a2 transcript treated with imatinib have lower and slower cytogenetic
and molecular responses than those with e14a2 transcript. They should be
considered a high-risk group that would most benefit from frontline
treatment with second-generation TKIs (2GTIKIs). Although few studies
have been published, similar significant differences in response rates
to 2GTKIs have been not reported. The e14a2 transcript seems to be a
favorable prognostic factor for obtaining s-DMR, irrespective of the TKI
received, and is also associated with a very high rate of TFR
maintenance. Indeed, patients with e13a2 transcript achieve a lower rate
of s-DMR and experience a higher probability of TFR failure. According
to most reported data in the literature, the type of transcript does not
seem to affect long-term outcomes of CML patients treated with TKIs. In
TFR, the e14a2 transcript appears to be related to favorable responses.
2GTKIs as frontline therapy might be a convenient approach in patients
with e13a2 transcript to achieve optimal long-term outcomes
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