scholarly journals Hemoglobin Changes during Long-Lasting Frontline Treatment with Tyrosine-Kinase Inhibitors in Patients with Chronic Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1486-1486
Author(s):  
Roberto Latagliata ◽  
Ida Carmosino ◽  
Ambra Di Veroli ◽  
Emilia Scalzulli ◽  
Gioia Colafigli ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Advisory Board ◽  
Secondary Resistance ◽  
Moderate Anemia ◽  
Frontline Treatment ◽  
The Impact

Abstract Introduction Chronic Myeloid Leukemia (CML) has become highly curable after introduction of Tyrosine-Kinase Inhibitors (TKIs). However, several side-effects have been reported with the prolonged use of TKIs: in particular, severe cardiovascular and pulmonary toxicities were observed with 2 nd generation TKIs (2G-TKIs), nilotinib and dasatinib. Imatinib is generally considered safer, even if some concerns were recently raised on its renal toxicity and occurrence of late anemia. Aims To evaluate the impact of imatinib compared to 2G-TKIs on the hemoglobin (Hb) levels in the long-lasting frontline treatment of CML patients. Methods From 1/2002 to 12/2015, 365 CML patients were diagnosed and treated frontline with TKIs in 2 different Centres in Italy: of them, 123 permanently discontinued the treatment before the 5 th year from the start due to intolerance (31 cases, 25.2%), primary resistance (41, 33.3%), secondary resistance (16, 13.0%), blastic evolution (4, 3.2%), unrelated death (12, 9.8%) or were lost to follow-up (19, 15.5%). At 5 years, the remaining 242 patients were still receiving frontline TKI treatment and were considered for the present analysis. Hb levels were recorded at baseline and thereafter every 12 months up to the 5 th year of treatment. Results As to frontline treatment, 186 patients (76.8%) received imatinib and 56 (23.2%) 2G-TKIs (nilotinib in 44 cases and dasatinib in 12, respectively). The main clinical features at diagnosis of the entire cohort and according to frontline treatment are reported in the table: median Hb value at baseline was significantly lower in patients treated with 2G-TKIs. Median Hb values at different time-points according to frontline treatment are reported in the Figure. In patients treated with imatinib, median Hb levels at 12 th (12.5 g/dl, IQR 11.6-13.5) and 60 th month (12.4 g/dl, IQR 11.4-13.3) were stable compared to baseline (12.8 g/dl, IQR 11.3-13.8) (p=0.248 and p=0.075, respectively). On the contrary, median Hb levels at 12 th (13.4 g/dl, IQR 12.2-14.3) and 60 th month (13.6 g/dl, IQR 12.0-14.6) showed a significant increase compared to baseline (11.8 g/dl, IQR 10.6-13.7) in patients treated with 2G-TKIs (p<0.001 in both cases). As a consequence, during the treatment median Hb values became significantly higher at any different time-point in patients treated with 2G-TKIs compared to patients treated with imatinib (p=0.005 at the 12 th month, p=0.010 at the 60 th month). At baseline, the rate of patients with mild to moderate anemia (Hb < 11 g/dl) was significantly lower in those treated with imatinib [34/186 (18.2%) vs 20/56 (35.7%) treated with 2G-TKIs, p=0.006]: at the 12 th month, no difference was observed [15/186 (8.0%) in patients treated with imatinib vs 3/56 (5.3%) in patients treated with 2G-TKIs, p=0.498], while at the 60 th months the rate of patients with mild to moderate anemia became significantly higher in those treated with imatinib [29/186 (15.6%) vs 2/56 (3.6%) treated with 2G-TKI, p=0.018]. Conclusions Present data highlight that long-lasting treatment with imatinib can have a negative late effect on erythropoiesis, with incomplete recovery of hemoglobin levels and occurrence of late anemia in about 15% of patients at the 60 th month of therapy.This possible adverse event, which is still unrecognized and seems very rare with 2G-TKIs, could affect quality of life and should be recognized in the long-term management of CML patients. Figure 1 Figure 1. Disclosures Latagliata: BMS Cellgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Martelli: Novartis: Other: advisory board; Gilead: Other: advisory board. Breccia: Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria.

scholarly journals The impact of introducing tyrosine kinase inhibitors on chronic myeloid leukemia survival: a population-based study

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Enza Di Felice ◽  
Francesca Roncaglia ◽  
Francesco Venturelli ◽  
Lucia Mangone ◽  
Stefano Luminari ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Population Based ◽  
Population Based Study ◽  
The Impact

scholarly journals PF401 IMMUNE SYSTEM AND CHRONIC MYELOID LEUKEMIA: THE IMPACT OF TYROSINE KINASE INHIBITORS

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 152-153
Author(s):  
R.S. Alves ◽  
S.E. McArdle ◽  
J. Vadakekolathu ◽  
A.C. Gonçalves ◽  
P. Freitas-Tavares ◽  
...  
Keyword(s):  
Immune System ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
The Impact

scholarly journals The Impact of Tyrosine Kinase Inhibitors on Fatherhood in Patients with Chronic Myeloid Leukemia, a Single Institution Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4613-4613
Author(s):  
Mohammad Abu-Tineh ◽  
Elrazi Awadelkarim A Ali ◽  
Awni Alshurafa ◽  
Khalid Alhaj ◽  
Yousef Hailan ◽  
...  
Keyword(s):  
Congenital Anomaly ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Inclusion Criteria ◽  
Male Patients ◽  
Tki Treatment ◽  
The Impact

Abstract Introduction Following the launch of the TKI's (tyrosine kinase inhibitors) for the treatment of CML (Chronic myeloid leukemia), establishing its significant control over the disease as evident by multiple studies such as the population based Swedish CML registry reporting that Patients reaching 70 years of age had a relative survival close to 1.0 compared to the normal population with the same age. Consequently, other dimensions have emerged regarding the safety of treatment, particularly the effect on Male fatherhood. This study was conducted to review the real-life data on the effect of TKI on the fatherhood of male patients in the National Center of cancer care and research (NCCCR) in Qatar in the period of 1st of January 2005 - 1st of January 2020. Up to our knowledge, this is the first study addressing the effect of TKI on fatherhood in patients with CML. Methods A single-center study, conducted a mixed-design (retrospective+ phone interviews) with CML male patients in the Chronic or accelerated phase, being followed up in NCCCR, evaluating the effect of Imatinib, Dasatinib, nilotinib, on their fatherhood whether they are taking it as first, a second, or third line of treatment. Inclusion Criteria: -Male patient diagnosed with CML, in Chronic or accelerated phase; 18 years of age or older and actively receiving tyrosine kinase inhibitors including (Imatinib, dasatinib, nilotinib) with the following: -Patients with no known issues with regards to fertility, (fertility is intact) will be included in the study. -Patients who developed fertility issues after the diagnosis of CML and starting TKI's. He has been evaluated by an andrologist and his evaluation concluded its TKI related. Exclusion criteria: -Patients with other MPNS. -Patients not fulfilling inclusion criteria as follow: -Patient known to have infertility before the diagnosis of CML -Patient with infertility after Diagnosis of CML: If a clear underlying cause, not TKI related, will be excluded from the studyif no evaluation was done for infertility and it is not clear whether the infertility is related to an underlying cause or TKI and no proper evaluation by andrologist done excluded from this study The mother has documentation by gynecologist for infertility, or after examining the abortion, still-birth, or IUFD and checking the chromosomal analysis (any mother related cause whether endogenous or exogenous has been excluded) Results: 150 patients were interviewed to be included in the study, 22 (14%) patients had concerns related to medications safety and possible transmission of the disease, 33 (22%) patients had their families completed by the time of diagnosis. 26 patients have met the inclusion criteria, median age around 44 years, median age at diagnosis was 33.5. 100% were in chronic phase, 42.3% were on imatinib, 34.6% on Nilotinib, and 23.1% on Dasatinib. The median TKI exposure period before pregnancy was 3 years. Median age at first conception post TKI treatment is 36, with a median duration of TKI treatment around 7 years. offspring's total number was 43, 97.6% were full-term, had a normal delivery, and normal average weight at delivery. No stillbirths, fetal demise, or congenital anomaly were reported. All offspring had normal development and growth. Median age of children after CML diagnosis around 7 years. No reports of any CML-related cancer in all the offspring Conclusion: Around 98% of male CML patients taking imatinib, Dasatinib, Nilotinib had their offspring born normally with no delivery complications noted, all had no congenital anomaly, had normal growth and development, and no CML-related cancers were diagnosed. Further studies with a larger sample size are required to shed light on the TKI outcome on fatherhood in CML patients. Nonetheless, a call for attention for better education to patients starting on TKI's addressing the possible psychological fear or concerns of having an unsatisfactory effect on their fertility/offspring, targeting better acceptance and adherence to treatment. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals First-generation vs second-generation tyrosine kinase inhibitors: which is best at diagnosis of chronic phase chronic myeloid leukemia?

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 228-236
Author(s):  
Vivian G. Oehler
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
First Generation ◽  
Second Generation ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
First Line ◽  
The Impact

Abstract In 2020, for the great majority of patients with chronic phase chronic myeloid leukemia (CML), life expectancy is unaffected by a diagnosis of CML because of the unparalleled efficacy of ABL-targeted tyrosine kinase inhibitors (TKIs) in halting disease progression. A wealth of choices exist for first-line treatment selection, including the first-generation TKI imatinib and the second-generation TKIs bosutinib, dasatinib, and nilotinib. How I select first-line therapy between first-generation and second-generation TKIs is discussed in the context of patient-specific CML disease risk, therapy-related risks, and treatment goals. Although rare, identifying patients with CML at higher risk for disease progression or resistance is important and influences first-line TKI selection. I review the impact of first-generation vs second-generation TKI selection on treatment response and outcomes; the ability to achieve, as well as the timing of, treatment-free remission; and the impact of specific TKIs on longer-term health.

scholarly journals Severe obesity in a patient on long-term treatment of chronic myeloid leukemia with imatinib: Body composition, associated disorders and outcome

2021 ◽  
Vol 2 (6) ◽  
Author(s):  
Jorge Illarramendi Illarramendi ◽  
◽  
María Angeles Goñi ◽  
Montserrat Alvarellos ◽  
Ana Zugasti ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Severe Obesity ◽  
Long Term Treatment ◽  
Hypopnea Syndrome ◽  
The Impact

Chronic Myeloid Leukemia (CML) is a highly curable malignancy with tyrosine kinase inhibitors (TKI) as target therapy. As treatment is usually prolonged, there is a need to improve our knowledge about the impact of comorbidities in this context. Severe obesity is among the common comorbidities in these patients. We present the case of a patient with morbid obesity and associated sleep apnea hypopnea syndrome who was succesfully treated during 14 years with imatinib, a cornerstone TKI for this disease. Visceral fat area was extremely elevated in this patient. Keywords: chronic myeloid leukemia; obesity; imatinib; sleep apnea hypopnea syndrome. Abbreviations: CML: Chronic Myeloid Leukemia; BMI: Body Mass Index; TKI: Tyrosine Kinase Inhibitors.

scholarly journals THE IMPACT OF TYROSINE KINASE INHIBITORS ON FATHERHOOD IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA, A SINGLE INSTITUTION EXPERIENCE

2021 ◽  
Vol 43 ◽  
pp. S15
Author(s):  
Mohammad Abu-Tineh ◽  
Awni Alshurafa ◽  
Elrazi Awadelkarim Hamid Ali ◽  
Yousef Hailan ◽  
Waail Rozi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Single Institution ◽  
The Impact

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

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