JAMA Oncology: Prognostic assessment of the deactivation of tyrosine kinase inhibitors in patients with chronic myeloid leukemia

Chronic granulocytic leukemia (CML) is caused by BCR-ABL1 tyrosine kinase, a product of the Philadelphia chromosome t (9;22) sublocation.
since the introduction of tyrosine kinase inhibitors (TKIs), the survival rate of patients with chronic granulocytic leukemia has increased.
TKIs are less toxic than previous treatments, they are associated with fatigue, depression, sleep disorders and diarrhea.
has shown that deactivating TKIs is safe and associated with the successful realization of treatment-free remission (TFR) in some patients.
, for patients with chronic myeloid leukemia, are there any characteristics associated with the successful deactivation of tyrosine kinase inhibitors, and are symptoms improving in patients after deactivation? A new study published recently on JAMA Oncology called Assment of Outcomes After Stopping Tyrosine Kinase Patients With Chronic Myeloid Leukemia A Nonrandomized Clinical Trial assessed molecular recurrence (MRec) and prognostics (PROs) reported by patients after CML patients deactivated TKI.
Study (LAST Study) is a forward-looking single-group non-randomized clinical trial that included 172 patients at 14 academic medical centers in the United States for at least three years from December 18, 2014 to December 12, 2016.
participants were adults with chronic CML who were well controlled with Imatini, Dasatini, Nilotini or Posutini.
analysis will be available from 13 August 2019 to 23 March 2020.
results and measurements of the study: the absence of major molecular reactions was detected through the central laboratory, and the prognosmation was monitored.
digital polymerase chain reaction (ddPCR) on samples not detected by BCR-ABL1 using standard real-time quantitative polymerase chain reaction (RQ-PCR).
172 patients included in the process, 89 were women (51.7%) and the middle age was 60 years (21-86 years).
171 patients for molecular analysis, 112 (65.5%) remained in the primary molecular response state and 104 (60.8%) received TFR.
BCR-ABL1 is not detected by ddPCR or RQ-PCR during TKI suspension and 3 months, independently associated with MREC.
RQ-PCR detects a molecular recurrence rate of 50.0% (14 out of 28) in patients with BCR-ABL1, and RQ-PCR does not detect BCR-ABL1 but ddPCR detects BCR-A BL1 was 64.3% (36 out of 56 cases) and 10.3% (9 out of 87) (P.001) were patients who did not detect BCR-ABL1 in ddPCR and RQ-PCR.
112 patients who received TFR at 12 months, 90 (80.4%) had clinically significant improvements in fatigue symptoms and 39 (34.8%) had clinically significant improvements in depression 98 (87.5%) had clinically significant improvements in diarrhea, 24 (21.4%) had clinically significant improvements in sleep disorders, and 5 (4.5%) had clinically significant improvements in pain intervention.
14.0% of patients (24 out of 171) had at least moderate sleep disorders before the probability of re-occurrence of molecules, treatment-free remission (TFR) and molecular recurrence (MRec) was deactivated.
average sleep disorder score improved after TKI was deactived, and the improvement was ongoing.
12 months, the sleep disorder score improved clinically in 21.4% of patients (24 out of 112) in TFR.
sleep disorder scores worsened after restarting TKI treatment, although they appeared to improve again over time.
At 6 and 12 months, patients who stopped tyrosine kinase inhibitors (TKI) and restarted TKI reported changes in average outcomes despite previous reports of an increase in musculoskeletal pain (TKI withdrawal syndrome) after drug withdrawal, but few patients in this study reported an increase in pain and an impact on their daily lives.
previous studies, adverse events of musculoskeletal pain were reported by clinicians, and the correlation between clinically reported adverse events and benefits was moderate.
other types of data will also be used in future analyses to investigate pain and TKI withdrawal syndrome, the researchers said.
, this non-randomized clinical trial showed that deactivation of tyrosine kinase inhibitors was safe and feasible and associated with the reported prognostic improvements in patients.
: Atallah E, Schiffer CA, Radich JP, et al. Assessment of Outcomes After Stopping Tyrosine Kinase ResOrs Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial. JAMA Oncol. Published online November 12, 2020. doi:10.1001/jamaoncol.2020.5774MedSci Original Source: MedSci Original Copyright Notice: All on this website state "Source: Met Medical" or "Source: MedSci Original" text, images and audio and video materials, copyrights are owned by Metz Medicine, without authorization, no media, website or individual may reproduce, authorized to reproduce with the words "Source: Mets Medicine".
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