Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second- and third-generation tyrosine kinase inhibitors

Caocci, Giovanni; Mulas, Olga; Annunziata, Mario; Luciano, Luigiana; Abruzzese, Elisabetta; Bonifacio, Massimiliano; Orlandi, Ester; Albano, Francesco; Galimberti, Sara; Iurlo, Alessandra; Pregno, Patrizia; Sgherza, Nicola; Martino, Bruno; Binotto, Gianni; Castagnetti, Fausto; Gozzini, Antonella; Bocchia, Monica; Fozza, Claudio; Stagno, Fabio; Simula, Maria Pina; Gregorio, F. De; Trawinska, Malgorzata Monika; Scaffidi, Luigi; Elena, Chiara; Attolico, Imma; Baratè, Claudia; Cattaneo, Daniele; Pirillo, Francesca; Gugliotta, Gabriele; Sicuranza, Anna; Molica, Matteo; Nasa, Giorgio La; Foà, Robin; Breccia, Massimo

doi:10.1016/j.ijcard.2019.10.036

Cited by 22 publications

(21 citation statements)

References 11 publications

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“…In the EN-ESTnd trial, comparing Nilotinib and Imatinib in 564 CML patients in first line, all grade infection rate was 17 % in the Nilotinib versus 14 % in the Imatinib arm, with grade 3/4 infections rate in the Nilotinib cohort less then 1% [75]. In conclusion, Nilotinib seems to be an antiinflammatory agent with a good infective safe profile; these features could make it, in our opinion, a good candidate in the COVID-19 setting; nevertheless, we have to consider its high rate of cardiovascular complications seen in CML [76,77] that could be the consequence of the inflammatory endothelial damage, as shown by higher IL6 and lower IL10 levels in CML patients presenting cardiovascular events [78]. At the moment, no studies with Nilotinib in COVID-19 have been registered in the "clinical trials.gov" website.…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 80%

The CoV-2 outbreak: how hematologists could help to fight Covid-19

Galimberti

Baldini

Baratè³

et al. 2020

Pharmacological Research

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COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in the light of their possible application in COVID-19. The most promising drugs might be: Ruxolitinib, a JAK1/2 inhibitor, with a rapid and powerful anticytokine effect, tyrosine kinase inhibitors (TKIs), with their good anti-inflammatory properties, and perhaps the anti-Cd26 antibody Begelomab. We also present immunological data from gene expression experiments where TKIs resulted effective anti-inflammatory and pro-immune drugs. A possible combined treatment algorithm for COVID-19 is here proposed.

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Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 80%

The CoV-2 outbreak: how hematologists could help to fight Covid-19

Galimberti

Baldini

Baratè³

et al. 2020

Pharmacological Research

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“…We and others have demonstrated diminished linear growth during long-term treatment with these agents [13][14][15][16][17]. While the incidence of cardiovascular disease such as myocardial infarction, peripheral arterial disease and stroke is elevated in adults with CML treated with second and third generation TKIs, no studies have systematically examined these effects in children [18,19]. In Ph + ALL, the risk of late effects from combining TKIs and chemotherapy may be increased compared to that of chemotherapy or TKIs alone.…”

Section: Introductionmentioning

confidence: 99%

Patterns of surveillance for late effects of BCR-ABL tyrosine kinase inhibitors in survivors of pediatric Philadelphia chromosome positive leukemias

et al. 2021

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Background Targeted anticancer therapies such as BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, little is known about long-term risks of TKIs in children. Exposure-based survivorship guidelines do not include TKIs, thus surveillance practices may be variable. Methods We retrospectively examined surveillance for cardiac and endocrine late effects in children receiving TKIs for Ph + leukemias, diagnosed at < 21 years between 2000 and 2018. Frequency of echocardiogram (ECHO), electrocardiogram (EKG), thyroid stimulating hormone (TSH), dual-energy x-ray absorptiometry (DXA), and bone age testing were abstracted. Descriptive statistics were stratified by leukemia type. Results 66 patients (CML n = 44; Ph + ALL n = 22) met inclusion criteria. Among patients with CML, ≥1 evaluation was done: ECHO (50.0%), EKG (48.8%), TSH (43.9%), DXA (2.6%), bone age (7.4%). Among patients with Ph + ALL, ≥1 evaluation was done: ECHO (86.4%), EKG (68.2%), TSH (59.1%), DXA (63.6%), bone age (44.4%). Over a median 6.3 and 5.7 years of observation, respectively, 2% of patients with CML and 57% with Ph + ALL attended a survivorship clinic. Conclusions Despite common exposure to TKIs in survivors of Ph + leukemias, patterns of surveillance for late effects differed in CML and Ph + ALL, with the latter receiving more surveillance likely due to concomitant chemotherapy exposures. Targeted therapies such as TKIs are revolutionizing cancer treatment, but surveillance for late effects and referral to survivorship clinics are variable despite the chronicity of exposure. Evidence based guidelines and longer follow-up are needed.

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“…The choice of treatment for elderly patients resistant or intolerant to previous line(s) with a TKI is generally more difficult than in younger subjects, owing to the baseline comorbidities often present in elderly patients 17 and to the specific safety profile of second‐ and third‐generation TKIs employed as second or a subsequent line of treatment. These toxicities, in particular cardiovascular toxicities related to treatment with nilotinib and ponatinib or pleural effusions related to treatment with dasatinib, 18–20 are in many cases of difficult management in patients with pre‐existing cardiovascular and/or pulmonary diseases.…”

Section: Discussionmentioning

confidence: 99%

Bosutinib in the real‐life treatment of chronic myeloid leukemia patients aged >65 years resistant/intolerant to previous tyrosine‐kinase inhibitors

Latagliata

Attolico

Trawinska

et al. 2021

Hematological Oncology

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To evaluate the role of bosutinib in elderly patients aged >65 years with chronic myeloid leukemia (CML), a real‐life cohort of 101 chronic‐phase CML patients followed up in 23 Italian centers and treated with bosutinib in second or a subsequent line was retrospectively evaluated. Starting dose of bosutinib was 500 mg/day in 25 patients (24.8%), 400 mg/day in 7 patients (6.9%), 300 mg/day in 33 patients (32.7%), 200 mg/day in 34 patients (33.6%), and 100 mg/day in 2 patients (2.0%). Grade 3/4 hematological toxicity occurred in 7/101 patients (6.9%) and grade 3/4 extra‐hematological toxicity in 19/101 patients (18.8%). Permanent bosutinib discontinuation due to toxicity was needed in 12 patients (11.9%). Among the 96 patients evaluable for response, 74 (77.0%) achieved a complete cytogenetic response (CCyR), while 64 of these 74 patients in CCyR (66.6% of all 96 evaluable patients) also achieved a molecular response (MR) (major MR [MR 3.0] in 21 [21.8%], deep MR [MR 4.0/4.5] in 43 [44.8%]). The 3‐year event‐free survival and overall survival of the whole patients' cohort from bosutinib start were 60.9% (CI 95% 49.3–72.5) and 86.4% (CI 95% 77.2–95.6), respectively. Our real‐life data show that bosutinib is effective, with a favorable safety profile, also in elderly patients with important comorbidities and resistance and/or intolerance to previous tyrosine‐kinase inhibitor treatments. As a consequence, it could play a significant role in current clinical practice for frail patients.

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Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second- and third-generation tyrosine kinase inhibitors

Cited by 22 publications

References 11 publications

The CoV-2 outbreak: how hematologists could help to fight Covid-19

The CoV-2 outbreak: how hematologists could help to fight Covid-19

Patterns of surveillance for late effects of BCR-ABL tyrosine kinase inhibitors in survivors of pediatric Philadelphia chromosome positive leukemias

Bosutinib in the real‐life treatment of chronic myeloid leukemia patients aged >65 years resistant/intolerant to previous tyrosine‐kinase inhibitors

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