scholarly journals Clinical significance of dasatinib-induced pleural effusion in patients with de novo chronic myeloid leukemia

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Aya Nakaya ◽  
Shinya Fujita ◽  
Atsushi Satake ◽  
Takahisa Nakanishi ◽  
Yoshiko Azuma ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Clinical Features ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Late Onset ◽  
Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Treatment Agent

Dasatinib is currently approved for clinical use as a first-line treatment agent for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical trials have been performed to evaluate dasatinibinduced PE following first-line therapy. We investigated the incidence and clinical features of dasatinib-induced PE following first-line therapy in Japanese CML patients of real world clinical practice settings. Among 22 patients, the median age of PEpositive patients was higher than that of PEnegative patients. Major molecular response was achieved in 75% of PE-positive patients and 50% of PE-negative patients. Most patients developed PE more than 1 year after treatment. Appearance of PE is associated with better clinical response during dasatinib treatment, however it is developed at any time. Elderly and high-risk patients tend to develop PE. The clinical features of dasatinib-induced PE following first-line therapy might be late onset and might not immediately follow the increasing of large granular lymphocyte.

scholarly journals Predictive value of early molecular response in patients with chronic myeloid leukemia treated with first-line dasatinib

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 291-294 ◽  
Author(s):  
David Marin ◽  
Corinne Hedgley ◽  
Richard E. Clark ◽  
Jane Apperley ◽  
Letizia Foroni ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
Transcript Level ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
First Line ◽  
Complete Cytogenetic Response ◽  
First Line Therapy ◽  
Line Therapy

Abstract Dasatinib is effective therapy for newly diagnosed patients with chronic myeloid leukemia, but not all patients respond well. We analyzed the outcome of patients treated with dasatinib as first-line therapy to identify patients who are more likely to fare poorly. The 8.6% of patients who at 3 months had a BCR-ABL1/ABL1 ratio > 10% had a significantly worse 2-year cumulative incidence of complete cytogenetic response (58.8% vs 96.6%, P < .001) and molecular responses than the remaining patients with a lower transcript levels. The predictive value of the 3-month transcript level could be improved using the dasatinib-specific transcript level cut-offs, namely, 2.2%, 0.92%, and 0.57% for complete cytogenetic response, 3 log and 4.5 log reductions in the transcript level, respectively. The study was registered at www.clinicaltrials.gov as #NCT01460693.

scholarly journals Deep and early molecular response induced by nilotinb in a newly diagnosed patient with chronic myeloid leukemia (CML)

2015 ◽  
Vol 7 (1S) ◽  
pp. 19-23
Author(s):  
Antonella Russo Rossi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Transcript Level ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Complete Hematologic Response ◽  
Level Reduction

We report a case of a patient with chronic myeloid leukemia diagnosed in January 2012 and treated with nilotinib 600 mg/die as first line therapy. Patient obtained a complete hematologic response (CHR) and improvement of splenomegaly in 2 weeks. In three months the patient obtained complete cytogenetic response (CCR) and an important transcript level reduction (less than 1%). According to the international recommendations, molecular analysis was performed every three months in a LABNET network laboratory. Treatment was never interrupted or reduced due to any adverse event. After 9 months patient achieved a major molecular response (MMR) and during evaluation a MR4 has been documented.

scholarly journals Efficacy and safety of Bosutinib in Patient with Chronic myeloid leukemia who was intolerant to DASTANIB,NILOTUNIB -Case report

2021 ◽  
Author(s):  
Abdullah Mohammad Arshad ◽  
mohamed yassin
Keyword(s):  
Case Report ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
Efficacy And Safety ◽  
Major Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Bosutinib is approved as first line therapy for treatment of chronic phase CML and also in patients who are either resistant or intolerant to previous TKI. We present a 59 year old male who was intolerant to 2 TKI but showed excellent hematological and major molecular response to Bosutinib.

Real-world response monitoring and tolerability of imatinib-treated chronic myeloid leukemia patients captured in a retrospective research registry.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6583-6583
Author(s):  
David D. Stenehjem ◽  
Frederick S. Albright ◽  
Min Amy Guo ◽  
Lei Chen ◽  
Karina Raimundo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Real World ◽  
Myeloid Leukemia ◽  
Response Monitoring ◽  
Molecular Testing ◽  
Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Impact

6583 Background: Monitoring tolerability and response to imatinib (IM) is an important aspect of chronic myeloid leukemia (CML) management. The objective of this study is to assess real-world tolerability and response monitoring in IM treated CML patients (pts). Methods: A comprehensive retrospective outcomes research registry of CML pts was created from the University of Utah electronic health record system. Study inclusion was limited to pts diagnosed with CML in chronic phase in 2001 to 2010 and treated with IM as a first-line therapy. Utilization and outcome of cytogenetic and molecular testing within 18 months of IM initiation, rates of adverse drug events (ADEs), and therapy modifications were evaluated by chart review. Results: A total of 92 pts were treated with IM as first-line therapy. Within the first 18 months of treatment, cytogenetic testing was recorded in 45 pts (49%) and of these 33 pts (73%) achieved a complete cytogenetic response (CCyR) in a median of 241 days (range: 110-542); molecular testing was completed in 48 pts (52%) and of these 24 pts (50%) achieved at least a major molecular response (MMR) in a median of 254 days (range: 99-546). Imatinib associated ADEs of any grade (n = 60) occurred in 42 (46%) pts resulting in dose reductions in 15 pts (36%) in a median of 77 days and discontinuation of IM occurred in 9 (21%) pts in a median of 130 days. The IM dose was increased to >400 mg in 21 (23%) pts in a median of 457 days (range: 21-2112). Of pts diagnosed between 2006 to 2010 (n = 34; 37%), 8 (25%) pts transitioned to dasatinib or nilotinib in a median of 397 days (range: 147 to 1057). Reasons for therapy change included physician documented suboptimal response or treatment failure (n = 5) and ADEs to IM (n = 3). Conclusions: Utilization of cytogenetic and molecular testing within 18 months of IM initiation was lower than the National Comprehensive Cancer Network or European LeukemiaNet CML guidelines would suggest. Further research is warranted to understand limited response monitoring and outcomes in non-monitored pts. The ADE rate was similar to clinical trial data. The impact of ADEs on subsequent treatment and outcomes in CML pts deserves further study.

Medical decision analysis for first-line therapy of chronic myeloid leukemia

2014 ◽  
Vol 55 (8) ◽  
pp. 1758-1767 ◽  
Author(s):  
Ursula Rochau ◽  
Gaby Sroczynski ◽  
Dominik Wolf ◽  
Stefan Schmidt ◽  
Annette Conrads-Frank ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Decision Analysis ◽  
Myeloid Leukemia ◽  
Medical Decision ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Medical Decision Analysis

scholarly journals Treatment Interruption and Regimen Change in Firstgeneration versus Second-generation Tyrosine Kinase Inhibitors used as First-line Therapy for Chronic Myeloid Leukemia

10.36469/9899 ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 181-191
Author(s):  
Melea A. Ward ◽  
Gang Fang ◽  
Gang Fang ◽  
Kristy L. Richards ◽  
Christine M. Walko
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Treatment Interruption ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Treatment Interruptions ◽  
Regimen Change

Background: Research has shown that treatment interruptions are associated with worse failure-free survival in chronic myeloid leukemia (CML); however they are commonly used in clinical trials to manage adverse events. Objectives: This study assessed the comparative rates of treatment interruption and regimen change between patients initiating first-line therapy with a first-generation tyrosine kinase inhibitor (1GTKI) imatinib versus second-generation TKI (2GTKI), dasatinib or nilotinib, for the treatment of CML in clinical practice. Methods: This was a retrospective cohort study using the Humana Research Database. Patients with CML who were between the ages of 18 and 89 and newly initiated 1GTKI or 2GTKI therapy between June 1, 2010 and December 31, 2011 were included. Treatment interruption and regimen change were compared using multivariable Cox proportional hazard regression models. Treatment interruption was defined as a gap in any TKI pharmacy claim that was longer than an allowable refill gap plus days’ supply from the previous TKI medication claim. Regimen change was defined as 1) a prescription claim for a different TKI therapy, or 2) increase in dose for the same medication. Results: 368 patients met the inclusion criteria: 1GTKI n=237, 2GTKI n=131. Patients initiating therapy with a 2GTKI had a 48% higher risk of treatment interruption versus patients initiating therapy with a 1GTKI (hazard ratio=1.48, 95% confidence interval 1.08-2.02). The time to treatment interruption was significantly longer in patients initiating therapy with a 1GTKI. Approximately 19% of patients had a regimen change, but there were no differences in rates of regimen changes between the two generations. Conclusions: In this study from a large single health plan population, treatment interruptions were more common among patients initiating therapy with a 2GTKI, yet regimen change rates did not vary by generation of TKI. Future research should assess reasons for treatment interruption and investigate these associations in other populations.

Efficacy and safety of aspacytarabine (BST-236) as a single-agent, first-line therapy for patients with acute myeloid leukemia unfit for standard chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7007-7007
Author(s):  
Jessica K. Altman ◽  
Jamie Koprivnikar ◽  
James K. McCloskey ◽  
Vamsi Kota ◽  
Olga Frankfurt ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
De Novo ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
Standard Chemotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
De Novo Aml

7007 Background: Aspacytarabine (BST-236) is a prodrug of cytarabine, the backbone of acute myeloid leukemia (AML) standard of care chemotherapy, associated with toxicity which precludes its administration in older patients and patients with comorbidities. Aspacytarabine is inactive in its intact prodrug form until cytarabine is gradually released at pharmacokinetics which decrease the systemic exposure to peak toxic cytarabine levels, resulting in reduced systemic toxicity and relative sparing of normal tissues, enabling therapy with high cytarabine doses to patients otherwise unfit to receive it. Methods: A phase 2b open-label, single-arm study to evaluate the efficacy and safety of aspacytarabine as a first-line single-agent therapy in newly-diagnosed AML patients unfit for standard chemotherapy (NCT03435848). Aspacytarabine is administrated at 4.5 g/m2/d (containing 3 g/m2/d cytarabine) in 1-2 induction and 1-3 consolidation courses, each consisting of 6 daily 1-hour infusions. Patients with secondary AML, prior hypomethylating agent (HMA) therapy, and therapy-related AML, are eligible. Results: To date, in the ongoing study, 46 newly-diagnosed AML patients unfit for standard chemotherapy (median age 75 years) were treated with aspacytarabine and completed 1-4 courses of 4.5 g/m2/d aspacytarabine, including 26 patients (63%) with de novo AML and 17 (37%) with secondary AML. Six patients (13%) were previously treated with HMA (median 12 courses). The baseline median bone marrow blasts was 52%, and 54% and 29% of patients had adverse or intermediate European LeukemiaNet (ELN) score, respectively. Twenty (43%) patients had ECOG 2. Aspacytarabine is safe and well-tolerated in repeated-course administration. Grade > 2 drug-related adverse events include mainly hematological events and infections. The 30-day mortality rate is 11%. Of 43 patients evaluable for efficacy analysis to date, 15 patients (35%) reached a complete remission (CR) following 1 (13 patients) or 2 (2 patients) induction courses, all with complete hematological recovery (median 27.5 days, range 22-39 days). The CR rates in de novo AML patients and patients with adverse ELN score are 46% and 33%, respectively. Of the 11 patients evaluable to date for minimal residual disease (MRD) flow cytometry test, 8 are MRD negative (73%). While aspacytarabine treatment consists of a limited number of courses, median duration of response and median overall survival for responders are not reached at 12 and 24 months, respectively (end of follow up). Updated results will be presented at the meeting. Conclusions: The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone. Clinical trial information: NCT03435848.

scholarly journals Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis

2017 ◽  
Vol 143 (7) ◽  
pp. 1225-1233 ◽  
Author(s):  
Andreas Hochhaus ◽  
Franҫois-Xavier Mahon ◽  
Philipp le Coutre ◽  
Ljubomir Petrov ◽  
Jeroen J. W. M. Janssen ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy
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