Novel Score-based Decision Approach in Chronic Myeloid Leukemia Patients After Acute Toxic Imatinib-induced Liver Injury

Abstract

The tyrosine kinase inhibitor (TKI) imatinib in rare cases can cause acute toxic hepatitis, hepatic failure, and death. Currently, the choice of further chronic myeloid leukemia (CML) therapy in patients after acute hepatotoxicity is still a difficult question, which requires a complex individual approach based on the clinical guidelines of adverse event management. Data about the further follow-up strategy approach in patients with CML after acute toxic imatinib-induced liver injury are of concern, and at times controversial. In addition, one of the questions is about the necessity and safety of the imatinib therapy resumption after acute hepatotoxicity. In some publications, imatinib resumption without the recurrence of hepatotoxicity has been discussed; in others, imatinib resumption with the recurrence of imatinib hepatotoxicity has been mentioned. There are a few publications about the experience of administration of the second-line TKIs after acute imatinib hepatotoxicity. There are no clear data on which factors the physician’s decision should be based on in patients with CML after acute toxic imatinib-induced liver injury. Imatinib should be restarted or withdrawn, when and for whom second-line therapy should be started. The physician’s decision is usually based on the published data of similar cases, personal experience, and the severity of hepatotoxicity. We have discussed the clinical guidelines devoted to the peculiarities of the patient’s management after acute toxic imatinib-induced hepatitis and main strategy approaches. A complex score-based decision algorithm for choosing the further strategy approach after acute toxic imatinib-induced hepatitis in patients with CML has been presented. The following parameters should be assessed: the grade of hepatotoxicity reaction, the presence of liver transplantation or imatinib-induced liver cirrhosis and its possible pathogenetic mechanism, the presence of early molecular response (EMR) to imatinib therapy defined as three-month BCR-ABL1 ≤10% according to the international scale ( BCR-ABL1 IS ) or/and six-month BCR-ABL1 IS <1%; and the presence of the offender concomitant drug that probably caused the drug interaction with imatinib and the presence of viral hepatitis reactivation identified by polymerase chain reaction (PCR).

Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia

“… 4 To date, more than 25 clinical cases of the first generation BCR-ABL TKI imatinib-induced hepatitis have been reported. 5 , 6 As for the new-generation BCR-ABL TKIs, ponatinib therapy can cause rare instances of clinically apparent liver disease and even death, 7 , 8 , 9 prompting the FDA to issue a boxed warning. Severe liver injury was also reported in patients with CML treated with nilotinib and dasatinib.…”

“…Unfortunately, BCR-ABL TKIs are no exception . To date, more than 25 clinical cases of the first generation BCR-ABL TKI imatinib-induced hepatitis have been reported . As for the new-generation BCR-ABL TKIs, ponatinib therapy can cause rare instances of clinically apparent liver disease and even death, prompting the FDA to issue a boxed warning.…”

Medium-mass Molecules in Plasma of Patients at Different Stages of Chronic Myeloid Leukemia Progression

“…Цілком очевидно, що на вміст МСМ у плазмі крові впливають і токсичні ефекти медикаментозного лікування, і порушення дезінтоксикаційної функції печінки і видільної системи [3,18,19,26]. Результати досліджень низки авторів свідчать, що збільшення проявів інтоксикаційного синдрому у пацієнтів із ХМЛ, окрім генетичних порушень, впливу іонізуючого опромінен-ня під час обстежень, відіграє певну роль у виникненні резистентності до лікування [5,8,12,29,30,34].…”

Recent advances targeting C‐C chemokine receptor type 2 for liver diseases in monocyte/macrophage

“…Acute hepatic injury is a common disease in clinical practice, usually caused by chemical toxicant, drug, alcohol and infection, which will develop into an end‐stage liver disease if not treated effectively 32‐35 …”