Concomitant use of Tyrosine-kinase Inhibitor and Mepolizumab in Asthma secondary to Chronic Myeloid Leukemia with hypereosinophilia

Author(s):  
Antonio Gidaro ◽  
Emanuele Salvi ◽  
Maria Cristina Carraro ◽  
Roberta Simona Rossi ◽  
Roberto Castelli

Introduction: Asthma and hypereosinophilia have been treated with different therapeutics in the past. Some of them appear to be more effective in symptoms resolution and decreasing eosinophilic count. Case Presentation: We report here an unusual case of asthma with hypereosinophilia secondary to Chronic Myeloid Leukemia (CML) with high prevalence of eosinophilic infiltrate, treated simultaneously with an anti-IL-5 antibody (Mepolizumab) and Tyrosine-kinase Inhibitors (TKI: Imatinib and Bosutinib) for three years. The patient showed a promising reduction of pulmonary exacerbations and good control of CML without developing side effects. Conclusion: We hope that this finding could inspire further studies on the efficacy and safety of the concomitant use of anti-IL-5 and TKI.

2019 ◽  
Vol 4 (1-2) ◽  
pp. 41-45 ◽  
Author(s):  
Takeo Koshida ◽  
Sylvia Wu ◽  
Hitoshi Suzuki ◽  
Rimda Wanchoo ◽  
Vanesa Bijol ◽  
...  

Dasatinib is the second-generation tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia. Proteinuria has been reported with this agent. We describe two kidney biopsy–proven cases of dasatinib-induced thrombotic microangiopathy that responded to stoppage of dasatinib and using an alternate tyrosine kinase inhibitor. Certain specific tyrosine kinase inhibitors lead to endothelial injury and renal-limited thrombotic microangiopathy. Hematologists and nephrologists need to be familiar with this off-target effect of dasatinib.


2019 ◽  
Vol 20 (24) ◽  
pp. 6141 ◽  
Author(s):  
Luana Bavaro ◽  
Margherita Martelli ◽  
Michele Cavo ◽  
Simona Soverini

Chronic myeloid leukemia (CML) is characterized by the presence of the BCR-ABL1 fusion gene, which encodes a constitutive active tyrosine kinase considered to be the pathogenic driver capable of initiating and maintaining the disease. Despite the remarkable efficacy of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1, some patients may not respond (primary resistance) or may relapse after an initial response (secondary resistance). In a small proportion of cases, development of resistance is accompanied or shortly followed by progression from chronic to blastic phase (BP), characterized by a dismal prognosis. Evolution from CP into BP is a multifactorial and probably multistep phenomenon. Increase in BCR-ABL1 transcript levels is thought to promote the onset of secondary chromosomal or genetic defects, induce differentiation arrest, perturb RNA transcription, editing and translation that together with epigenetic and metabolic changes may ultimately lead to the expansion of highly proliferating, differentiation-arrested malignant cells. A multitude of studies over the past two decades have investigated the mechanisms underlying the closely intertwined phenomena of drug resistance and disease progression. Here, we provide an update on what is currently known on the mechanisms underlying progression and present the latest acquisitions on BCR-ABL1-independent resistance and leukemia stem cell persistence.


2020 ◽  
Vol 9 (11) ◽  
pp. 3692
Author(s):  
Matteo Dragani ◽  
Giovanna Rege Cambrin ◽  
Paola Berchialla ◽  
Irene Dogliotti ◽  
Gianantonio Rosti ◽  
...  

Successful discontinuation of tyrosine kinase inhibitors has been achieved in patients with chronic-phase chronic myeloid leukemia (CML). Careful molecular monitoring after discontinuation warrants safe and prompt resumption of therapy. We retrospectively evaluated how molecular monitoring has been conducted in Italy in a cohort of patients who discontinued tyrosine kinase inhibitor (TKI) treatment per clinical practice. The outcome of these patients has recently been reported—281 chronic-phase CML patients were included in this subanalysis. Median follow-up since discontinuation was 2 years. Overall, 2203 analyses were performed, 17.9% in the first three months and 38.4% in the first six months. Eighty-six patients lost major molecular response (MMR) in a mean time of 5.7 months—65 pts (75.6%) during the first six months. We evaluated the number of patients who would experience a delay in diagnosis of MMR loss if a three-month monitoring schedule was adopted. In the first 6 months, 19 pts (29.2%) would have a one-month delay, 26 (40%) a 2-month delay. Very few patients would experience a delay in the following months. A less intense frequency of monitoring, particularly after the first 6 months off treatment, would not have affected the success of treatment-free remission (TFR) nor put patients at risk of progression.


2012 ◽  
Vol 18 (4) ◽  
pp. 440-444 ◽  
Author(s):  
Prathima Prodduturi ◽  
Anamarija M Perry ◽  
Patricia Aoun ◽  
Dennis D Weisenburger ◽  
Mojtaba Akhtari

Nilotinib is a potent tyrosine kinase inhibitor of breakpoint cluster region-abelson (BCR-ABL), which has been approved as front-line therapy for newly diagnosed chronic myeloid leukemia in chronic phase and as second-line therapy after imatinib failure in chronic or accelerated phase chronic myeloid leukemia. Tyrosine kinase inhibitors have been associated with myelosuppression and grade 3 or grade 4 cytopenias are not uncommon in chronic myeloid leukemia patients treated with these drugs. There are a few reports of imatinib-associated bone marrow aplasia, but to our knowledge only one reported case of bone marrow aplasia associated with nilotinib. Herein, we report a 49-year-old male patient with chronic phase chronic myeloid leukemia, who developed severe bone marrow aplasia due to nilotinib. Possible mechanisms for this significant adverse drug reaction are discussed along with a review of literature.


Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Catherine C. Smith ◽  
Neil P. Shah

Abstract The 21st century ushered in the dawn of a new era of targeted therapeutics and a dramatic shift in the management of chronic-phase chronic myeloid leukemia (CP-CML) patients. Groundbreaking scientific and translational studies have led to the rapid development and approval of several effective BCR-ABL tyrosine kinase inhibitors (TKIs). In the United States, there are currently 3 approved BCR-ABL TKIs for newly diagnosed CP-CML patients. It is anticipated that clinical outcomes will continue to improve as more TKIs that address unmet medical needs are approved. However, to achieve this goal, it is critical to carefully monitor and optimally manage patients. To this end, the latest seminal clinical trial results of approved and investigational BCR-ABL TKIs and some of the salient unique features of each of these agents are summarized herein.


2021 ◽  
Vol 162 (32) ◽  
pp. 1297-1302
Author(s):  
Júlia Weisinger ◽  
Ilona Tárkányi ◽  
Eid Hanna ◽  
Ágnes Kárpáti ◽  
Zsolt Nagy ◽  
...  

Összefoglaló. Bevezetés: A krónikus myeloid leukaemia a diagnosztika fejlődésének és a tirozin-kináz-gátlók bevezetésének köszönhetően az elmúlt évtizedekben kiváló prognózisú betegséggé vált. Célkitűzés: A betegséggel kapcsolatos ismereteink nagy része klinikai vizsgálatokból származik, emiatt kiemelt szerepük van a nem szelektált beteganyagon végzett elemzéseknek. Módszer: Retrospektív elemzésünkben a Semmelweis Egyetem Belgyógyászati és Onkológiai Klinikáján 2003 és 2019 között tirozin-kináz-gátló kezelésben részesült betegek adatait tekintettük át. Eredmények: Klinikánkon összesen 88 beteg részesült terápiában, közülük 73 beteg az analízis időpontjában is kezelés alatt állt. A betegek 5 éves össztúlélése 86%, 5 éves progressziómentes túlélése 70% volt. 9 beteg halt meg, közülük 2 betegnél a halál oka a progrediáló alapbetegség volt. 38 betegnél volt szükség az első vonalban terápiaváltásra, a váltás oka akkor elsősorban az elégtelen terápiás válasz volt. A későbbi terápiaváltásokra elsősorban intolerancia miatt került sor. Az első vonalban a betegek több mint fele major molekuláris választ ért el, a jelenlegi kezelés mellett a betegek 85%-ánál major molekuláris választ detektáltunk. Megbeszélés: Adataink alapján az intézményünkben kezelt betegek túlélése és a betegek által elért terápiás válasz megfelel a nemzetközi adatoknak. Következtetés: Mivel nem válogatott beteganyagról van szó, a kapott eredmények pontosabb képet adhatnak a krónikus myeloid leukaemia tirozin-kináz-gátlóval történt kezelésének eredményeiről. Orv Hetil. 2021; 162(32): 1297–1302. Summary. Introduction: As a result of advances in diagnostic techniques and the introduction of tyrosine kinase inhibitors, the prognosis of chronic myeloid leukemia has improved over the last decades. Objective: Most of our knowledge about chronic myeloid leukemia results from clinical trials, therefore data derived from non-selected patient population is substantial. Method: Data of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors at the Department of Internal Medicine and Oncology, Semmelweis University, between 2003 and 2019 were analysed retrospectively. Results: 88 patients received treatment, 73 patients were on therapy at the time of the analysis. Overall survival at 5 years was 86%, progression-free survival at 5 years was 70%. 9 patients died, 2 of them due to progressive disease. 38 patients needed 2nd line therapy, the main reason of treatment change was failure of therapy. Subsequent treatment modifications were conducted mostly because of intolerance. More than half of the patients on 1st line treatment reached major molecular response and 85% of the patients on treatment at the end of the analysis are in major molecular response. Discussion: Based on our data, survival and therapeutic response of patients in our center are similar to the international results. Conclusion: This analysis provides real-world data about treatment results of chronic myeloid leukemia in the tyrosine kinase inhibitor era. Orv Hetil. 2021; 162(32): 1297–1302.


Author(s):  
Andreia D. MENEZES ◽  
Nelson A. FRAIJI

Objectives: To evaluate the conditions of use of tyrosine kinase inhibitors and adherence by patients with chronic myeloid leukemia treated at a public hematology institution. Methods: This was an observational and cross-sectional study carried out from December 2015 to April 2016. Data collection was carried out through interviews with standardized questionnaires that assessed the socioeconomic and demographic profile, drug therapy and by the Morisky-Green test that assessed the green adherence. Patients over 18 years old who had been using one of the tyrosine kinase inhibitors for more than one month were included; imatinib, dasatinib or nilotinib and who signed the informed consert form, agreement to participate in study. Descriptive statistical analysis and chi-square test with Yates correction were performed. Results: 63 patients were interviewed, with a mean age of 50 years with a standard deviation of 15.95. being 60% men. As for knowledge about the aspects related to the use of inhibitors: 95.2% took at the right time, 93.7% did not use other medications concomitantly, 63.5% kept it in an appropriate place and 97% of the patients received prior guidance from the doctor about the use. As for information about treatment, 90.5% knew the purpose of taking the medication, 60% did not know the time of use, 83% did not know what would happen if they stopped taking it and 73% believed they could stop the treatment at some point. Adherence to treatment was identified 46% of patients. Conclusion: No statistically significant differences were found between having or not adherence, when compared with the studied variables.


2016 ◽  
Vol 34 (36) ◽  
pp. 4323-4328 ◽  
Author(s):  
Aaron N. Winn ◽  
Nancy L. Keating ◽  
Stacie B. Dusetzina

Purpose There is substantial concern surrounding affordability of orally administered anticancer therapies, particularly for Medicare beneficiaries. We examined rates of initiation and adherence to tyrosine kinase inhibitors (TKIs) among Medicare beneficiaries with chronic myeloid leukemia (CML) with and without cost-sharing subsidies. We selected TKIs given their effectiveness and strong indication for use among patients diagnosed with CML. Patients and Methods Using SEER-Medicare data, we identified individuals diagnosed with CML from 2007 to 2011. We used Cox proportional hazards regression to assess time from diagnosis to TKI initiation. We used generalized estimating equations to examine treatment initiation within 180 days and TKI adherence among initiators. We defined adherence as at least 80% of days covered during the 6 months after TKI initiation. Results Among 393 individuals diagnosed with CML from 2007 to 2011, 68% initiated TKI treatment within 180 days after diagnosis. In multivariate analysis, individuals with cost-sharing subsidies, younger age, lower comorbidity, and later year of diagnosis were significantly more likely to initiate TKIs. Among TKI initiators, 61% were adherent; adherence was lower for individuals age 80 years or older versus 66 to 69 years. Conclusion Only 68% of Medicare beneficiaries with CML initiated TKI therapy within 6 months of diagnosis. Delayed initiation among individuals without cost-sharing subsidies suggests that out-of-pocket costs may be a barrier to timely initiation of therapy among individuals diagnosed with CML.


Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4839-4842 ◽  
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Dan Jones ◽  
Neeli Reddy ◽  
Susan O'Brien ◽  
...  

Abstract Mutations in codon 317 after treatment with imatinib and dasatinib have been reported. We reviewed patients with chronic myeloid leukemia and mutations after tyrosine kinase inhibitor (TKI) therapy. F317L was detected in 20, including 12/99 (12%) with mutation after imatinib failure, and 8/16 (50%) after dasatinib (P = .001). Median follow-up from mutation detection was 25 months. At the time of F317L, 8 patients were in chronic phase (CP), 6 in accelerated phase, and 6 in blast phase. There was no difference in characteristics between patients with or without F317L mutations, or with no mutations. A complete cytogenetic response was acheived in 3 of 6 patients treated with nilotinib, 2 of 2 with imatinib, and 0 of 3 with dasatinib. Survival of patients with F317L was similar to those with other mutations (P = .45). Patients in CP had better outcome, with a 2-year survival of 75%. F317L mutation is resistant to dasatinib but sensitive to other TKIs. The prognosis is dependent mostly on the disease stage.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5543
Author(s):  
Hyeok-Jae Jang ◽  
Young-Min Woo ◽  
Kazuhito Naka ◽  
Jong-Ho Park ◽  
Ho-Jae Han ◽  
...  

Previous studies have suggested that statins can be repurposed for cancer treatment. However, the therapeutic efficacy of statins in chronic myeloid leukemia (CML) has not yet been demonstrated. In this study, we retrospectively evaluated the outcomes of 408 CML patients who underwent imatinib therapy. The deep molecular response rates in patients treated with the statin/TKI combination were significantly higher than those in patients treated with TKI alone (p = 0.0016). The statin/TKI combination exerted potent cytotoxic effects against wild-type and ABL1 mutant CML, BaF3, and K562/T315I mutant cells. Furthermore, the statin/TKI combination additively inhibited the colony-forming capacity of murine CML-KLS+ cells in vitro. In addition, we examined the additive growth-inhibitory effects of the statin/tyrosine kinase inhibitor (TKI) combination against CML patient-derived CD34+ cells. The growth-inhibitory effects of the statin/imatinib combination against CD34+/CML primary cells were higher than those against CD34+/Norm cells (p = 0.005), suggesting that the combination of rosuvastatin and imatinib exerted growth-inhibitory effects against CML CD34+ cells, but not against normal CD34+ cells. Furthermore, results from RNA sequencing of control and statin-treated cells suggested that statins inhibited c-Myc-mediated and hematopoietic cell differentiation pathways. Thus, statins can be potentially repurposed to improve treatment outcomes in CML patients when combined with TKI therapy.


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