scholarly journals Long Term Response Evaluation of Newly Diagnosed Chronic Myeloid Leukemia Patients on Imatinib Mesylate in Indian Population over 12 Years

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5913-5913
Author(s):  
Tara Rajendran ◽  
Prasad Pramod Rane ◽  
Krishna Prasad
Keyword(s):  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Indian Population ◽  
Kinase Inhibitor ◽  
Molecular Response ◽  
Response Evaluation ◽  
Free Survival

INTRODUCTION There has been a quantum leap in the research of inhibitor drugs following the discovery of tyrosine kinase inhibitor (TKIs), Imatinib in the early 1990s. The development of Imatinib, the first BCR-ABL tyrosine kinase inhibitor revolutionized the long term outcome of Chronic Myeloid Leukemia (CML) patients. CML is one of the most common hematological malignancies diagnosed in India. The breathtaking success due to effectiveness and financial viability of Imatinib among Indian population even led to its sale in its generic formulations by pharmaceutical companies in India around early 2000s. METHODS This is a single-center retrospective observational study conducted among 232 CML patients diagnosed and followed up over 12 years from 2003 until 2015 at Kasturba Medical College and Hospital, Mangalore, Manipal University, Karnataka, India. We closely analyzed the handwritten files and the electronic medical records of each of 232 CML patients for their demographic details, symptoms, date of diagnosis, blood counts, bone marrow reports, spleen size at diagnosis, cytogenetic and molecular reports, date - dosage - change in dose - resistance - side-effects of Imatinib and outcome. Patients were followed up closely. Results Median age was 44 years (range, 10 -78 years). In the year of 2008-2012, 46.1% of patients diagnosed with CML. 66.4% were male and 33.6% were female. During the first evaluation of patients at the time of diagnosis, 90.9% of patients were in the chronic phase, 4.7% in accelerated phase and 4.3% in blast phase. 97.8% were started on Imatinib orally as first line. 176 (75.9) patients received 400 mg orally. Five patients chose not to be treated. The most common side effect of Imatinib among patients were as follows: abdominal pain (13.3%), fever (10.8%), general weakness (4.7%), blurred vision (4.7%), abdominal distention (3.4%) and joint pain (2.2%). Response to treatment with Imatinib was evaluated in terms of molecular response as measured by real-time RT Q-PCR. The 3.4% who failed to respond to Imatinib, 3.4% patients were started with second-generation TKI's (dasatinib, nilotinib, hyper CVAD cyclophosphamide, vincristine, Adriamycin and dexamethasone). The first choice for switching TKI therapy in 4 (1.7%) patients were dasatinib, in (3.1%) was nilotinib and only one patient had to use Hyper CVAD chemotherapy. Table has summarized the use of second-generation TKI's. One patient expired and 4 has progression. 181(78.0%) patients came throughout the year of 2015. Among all patients 200 (86.2%) are still alive with disease, 18 (7.8%) are alive without disease and 14 (6.0%) were expired. Overall survival (OAS) is 218 (96%) Progression free survival (86.78%). The median BCR ABL/ABL value at the end of the six months was 11% and at the end of the one year was 3.38%. Conclusion The introduction of Imatinib mesylate had phenomenal changes in the management of CML. Molecular response evaluation after six months can predict the subsequent molecular response and can also be used as a surrogate monitor of the marrow cytogenetic response to imatinib therapy in CML. We report a high overall (OAS) and progress free survival (PFR) rates with very less side effects. Table Disclosures No relevant conflicts of interest to declare.

A New Computational Method to Predict Long-Term Minimal Residual Disease and Molecular Relapse after TKI-Cessation in CML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3099-3099 ◽  
Author(s):  
Ingmar Glauche ◽  
Hendrik Liebscher ◽  
Christoph Baldow ◽  
Matthias Kuhn ◽  
Philipp Schulze ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
Molecular Response ◽  
Tki Treatment

Abstract Predicting minimal residual disease (MRD) levels in tyrosine kinase inhibitor (TKI)-treated chronic myeloid leukemia (CML) patients is of major clinical relevance. The reason is that residual leukemic (stem) cells are the source for both, potential relapses of the leukemicclone but also for its clonal evolution and, therefore, for the occurrence of resistance. The state-of-the art method for monitoring MRD in TKI-treated CML is the quantification of BCR-ABL levels in the peripheral blood (PB) by PCR. However, the question is whether BCR-ABL levels in the PB can be used as a reliable estimate for residual leukemic cells at the level of hematopoietic stem cells in the bone marrow (BM). Moreover, once the BCR-ABL levels have been reduced to undetectable levels, information on treatment kinetics is censored by the PCR detection limit. Clearly, BCR-ABL negativity in the PB suggests very low levels of residual disease also in the BM, but whether the MRD level remains at a constant level or decreases further cannot be read from the BCR-ABL negativity itself. Thus, also the prediction of a suitable time point for treatment cessation based on residual disease levels cannot be obtained from PCR monitoring in the PB and currently remains a heuristic decision. To overcome the current lack of a suitable biomarker for residual disease levels in the BM, we propose the application of a computational approach to quantitatively describe and predict long-term BCR-ABL levels. The underlying mathematical model has previously been validated by the comparison to more than 500 long-term BCR-ABL kinetics in the PB from different clinical trials under continuous TKI-treatment [1,2,3]. Here, we present results that show how this computational approach can be used to estimate MRD levels in the BM based on the measurements in the PB. Our results demonstrate that the mathematical model can quantitatively reproduce the cumulative incidence of the loss of deep and major molecular response in a population of patients, as published by Mahon et al. [4] and Rousselot et al. [5]. Furthermore, to demonstrate how the model can be used to predict the BCR-ABL levels and to estimate the molecular relapse probability of individual patients, we compare simulation results with more than 70 individual BCR-ABL-kinetics. For this analysis we use patient data from different clinical studies (e.g. EURO-SKI: NCT01596114, STIM(s): NCT00478985, NCT01343173) where TKI-treatment had been stopped after prolonged deep molecular response periods. Specifically, we propose to combine statistical (non-linear regression) and mechanistic (agent-based) modelling techniques, which allows us to quantify the reliability of model predictions by confidence regions based on the quality (i.e. number and variance) of the clinical measurements and on the particular kinetic response characteristics of individual patients. The proposed approach has the potential to support clinical decision making because it provides quantitative, patient-specific predictions of the treatment response together with a confidence measure, which allows to judge the amount of information that is provided by the theoretical prediction. References [1] Roeder et al. (2006) Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications, Nat Med 12(10):1181-4 [2] Horn et al. (2013) Model-based decision rules reduce the risk of molecular relapse after cessation of tyrosine kinase inhibitor therapy in chronic myeloid leukemia, Blood 121(2):378-84. [3] Glauche et al. (2014) Model-Based Characterization of the Molecular Response Dynamics of Tyrosine Kinase Inhibitor (TKI)-Treated CML Patients a Comparison of Imatinib and Dasatinib First-Line Therapy, Blood 124:4562 [4] Mahon et al. (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11(11):1029-35 [5] Rousselot 
et al. (2014) Loss of major molecular response as a trigger for restarting TKI therapy in patients with CP- CML who have stopped Imatinib after durable undetectable disease, JCO 32(5):424-431 Disclosures Glauche: Bristol Meyer Squib: Research Funding. von Bubnoff:Amgen: Honoraria; Novartis: Honoraria, Research Funding; BMS: Honoraria. Saussele:ARIAD: Honoraria; Novartis: Honoraria, Other: Travel grants, Research Funding; Pfizer: Honoraria, Other: Travel grants; BMS: Honoraria, Other: Travel grants, Research Funding. Mustjoki:Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Ariad: Research Funding; Novartis: Honoraria, Research Funding. Guilhot:CELEGENE: Consultancy. Mahon:NOVARTIS PHARMA: Honoraria, Research Funding; BMS: Honoraria; PFIZER: Honoraria; ARIAD: Honoraria. Roeder:Bristol-Myers Squibb: Honoraria, Research Funding.

Tyrosine kinase inhibitor nilotinib induced palmoplantar erythrodysesthesia: A rare case

2022 ◽  
pp. 107815522110724
Author(s):  
Muzeyyen Aslaner Ak ◽  
Pelin Ertop Doğan ◽  
Birsen Sahip
Keyword(s):  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Palmoplantar Erythrodysesthesia

Introduction Nilotinib is a second generation Tyrosine Kinase inhibitor (TKI) used in the treatment of Chronic Myeloid Leukemia (CML). The development of tyrosine kinase inhibitors has transformed chronic phase chronic myeloid leukemia from a disease with a poor prognosis to a treatable chronic disease. Long-term treatment with tyrosine kinase inhibitors means that patients must be clinically managed and monitored for years. While under Nilotinib tretament, the development of palmoplantar erythrodyesthesia is a very rare condition compared to other oncological drugs. Case report A 66-year-old male patient, who was diagnosed with chronic phase CML in 2019 had been placed under imatinib treatment . He had major molecular response loss in 2021, and was started on second generation TKI nilotinib 2  ×  400mg/day, considering his comorbidities. We present a case of a 66-year-old patient with CML who developed palmoplantar erythrodysesthesia on the 21st day starting nilotinib treatment. Conclusion It is important to manage the side effects that develop in long-term treatments. Adverse events can have a negative impact on patient compliance and quality of life and lead to poor clinical outcomes Our case is the first to develop PPE after beginning nilotinib use. We present this phenomenon to raise awareness and ignite a review of management strategies.In this case, we wanted to emphasize the importance of managing side effects.

scholarly journals Sequential Use of Second-Generation Tyrosine Kinase Inhibitor Treatment and Intensive Chemotherapy Induced Long-Term Complete Molecular Response in Imatinib-Resistant CML Patient Presenting as a Myeloid Blast Crisis

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Masaaki Tsuji ◽  
Tatsuki Uchiyama ◽  
Chisaki Mizumoto ◽  
Tomoharu Takeoka ◽  
Kenjiro Tomo ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Molecular Response ◽  
Complete Molecular Response

Myeloid blast crisis of chronic myeloid leukemia (CML-MBC) is rarely seen at presentation and has a poor prognosis. There is no standard therapy for CML-MBC. It is often difficult to distinguish CML-MBC from acute myeloid leukemia expressing the Philadelphia chromosome (Ph+ AML). We present a case in which CML-MBC was seen at the initial presentation in a 75-year-old male. He was treated with conventional AML-directed chemotherapy followed by imatinib mesylate monotherapy, which failed to induce response. However, he achieved long-term complete molecular response after combination therapy involving dasatinib, a second-generation tyrosine kinase inhibitor, and conventional chemotherapy.

scholarly journals Current event-free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia

Cancer ◽  
2010 ◽  
Vol 117 (2) ◽  
pp. 327-335 ◽  
Author(s):  
Aref Al-Kali ◽  
Hagop Kantarjian ◽  
Jianqin Shan ◽  
Roland Bassett ◽  
Alfonso Quintás-Cardama ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Inhibitor Therapy ◽  
Event Free Survival ◽  
Current Event ◽  
Free Survival ◽  
Tyrosine Kinase Inhibitor Therapy
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