PCN6 FACTORS INFLUENCING PHYSICIAN RECOMMENDATION FOR IMATINIB MESYLATE IN CHRONIC PHASE CHRONIC MYELOID LEUKEMIA (CML) PATIENTS

Introduction: Imatinib mesylate has become the choice of drug in the treatment of chronic myeloid leukemia. Objective: To study safety profile of Imatinib (specific inhibitor or bcrabl tryosne kinase protein) in Philadelphia chromosome t {(9:22), bcr-abl} positive chronic myeloid leukemia (CML) chronic phase patients. Materials and Methods: After IEC clearance, 36, BCR-ABL positive CML patients in the chronic phase of the disease were recruited. Imatinib mesylate (Gleevec, Novartis), was started (400mg daily) and followed up weekly in first month, two weekly till three months & monthly thereafter. Safety profile data, recorded in pre-designed proforma, were analyzed for time of onset, duration and severity of adverse effects. Causality relationship of recorded adverse events was established with imatinib therapy using WHO-UMC criteria. Results: A total of 222 adverse events were reported in 36 CML-CP patients over 12 months of follow up. Thrombocytopenia was the most commonly reported in 60% of the patients followed by musculoskeletal (17%), dermatological (16%), gastrointestinal disturbances (13%), body weight changes (11%), superficial edema (8%) and liver enzyme rise (4%). More than 80% events reported within months of therapy which persisted for less than 3 months in most of the cases. No treatment was needed in 68% of cases while therapy alteration was not needed in 88% of cases. Most of the reactions (60%) had probable relationship with the therapy. Conclusion: Imatinib was well tolerated, having only mild to moderate grade of toxicities, mostly within 3 months of therapy and most of them persisted for less than 3 months of duration, requiring only symptomatic treatment and drug withhold or dose decrement in only few cases. Keywords: Safety profile; imatinib; causality assessment; adverse events. DOI: 10.3126/hren.v9i1.4358Health Renaissance, 2011: Vol.9 No.1:24-30

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Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692117666190925115852 ◽

2020 ◽

Vol 17 (1) ◽

pp. 48-54

Author(s):

Reni Widyastuti ◽

Melva Louisa ◽

Ikhwan Rinaldi ◽

Riki Nova ◽

Instiaty Instiaty ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

Kinase Inhibitor ◽

Chronic Phase ◽

Kinase Domain ◽

Molecular Response ◽

Major Molecular Response ◽

Cross Sectional ◽

Imatinib Resistance

Background: Imatinib mesylate is the first tyrosine kinase inhibitor approved for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However, previous studies have shown that about 20-30% of patients eventually would develop resistance to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL kinase domain mutation. One of the most common and serious variations account for imatinib response is T315I of ABL1 gene. Objective: The study aimed to examine the association of T315I mutation with the ABL1 gene and its relation to major molecular response (MMR) achievement in CML patients. This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different possible variations in the ABL1 gene. Methods: This was a cross-sectional study on Indonesian CML patients in chronic phase. We analyzed 120 blood samples from patients in chronic phase who have received imatinib mesylate (IM) for ≥12 months. Results: There were no T315I, F311I, and F317L mutations found in this study. However, we found another variation, which was 36 substitutions from A to G at position 163816 of ABL1 gene (according to NG_012034.1). Conclusions: We found no T315I, F311I, and F317L mutations in this study. Our findings suggest that there might be other factors that influenced the MMR achievement in our study patients. However, there were 36 substitutions from A to G at position 163.816 (according to NG_012034.1) that needed further examination to explore the significance of this mutation in clinical practice.

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Imatinib mesylate induces hypophosphatemia in patients with chronic myeloid leukemia in late chronic phase, and this effect is associated with response

American Journal of Hematology ◽

10.1002/ajh.20778 ◽

2007 ◽

Vol 82 (5) ◽

pp. 394-395 ◽

Cited By ~ 31

Author(s):

S. Osorio ◽

A. García Noblejas ◽

A. Durán ◽

J.L. Steegmann

Keyword(s):

Chronic Myeloid Leukemia ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

Chronic Phase

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Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment

Blood ◽

10.1182/blood-2007-07-103523 ◽

2008 ◽

Vol 111 (3) ◽

pp. 1039-1043 ◽

Cited By ~ 152

Author(s):

Andreas Hochhaus ◽

Brian Druker ◽

Charles Sawyers ◽

Francois Guilhot ◽

Charles A. Schiffer ◽

...

Keyword(s):

Overall Survival ◽

Chronic Myeloid Leukemia ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Cytogenetic Response ◽

Interferon Α ◽

Imatinib Treatment ◽

Serious Adverse Events ◽

Response Level

Abstract Imatinib mesylate, a targeted inhibitor of BCR-ABL tyrosine kinase, is the standard of care for chronic myeloid leukemia (CML). A phase 2 trial of imatinib in late chronic-phase (CP) CML after interferon-α (IFNα) failure enrolled 532 patients, 454 with a confirmed diagnosis of CP CML. Median time from diagnosis was 34 months; median duration of imatinib treatment was 65 months. Cumulative best rates of major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were 67% and 57%, respectively. At the 5-year landmark, 184 (41%) of the 454 patients are in CCyR. At more than 6 years, 199 (44%) of the 454 patients remain on imatinib. Most responses occurred within 12 months of starting imatinib; however, some patients achieved initial MCyR and CCyR more than 5 years after imatinib initiation. Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) and overall survival at 6 years were 61% and 76%, respectively. Both freedom from progression to AP/BP and overall survival (OS) were associated with cytogenetic response level at 12 months. No increase in rates of serious adverse events was observed with continuous use of imatinib for up to 6.5 years, compared with earlier time points. Imatinib continues to be an effective and safe therapy for patients with CP CML after failure of IFN.

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OCCURRENCE OF SECONDARY MALIGNANCIES IN CHRONIC MYELOID LEUKEMIA DURING THERAPY WITH IMATINIB MESYLATE-SINGLE INSTITUTION EXPERIENCE

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2015.003 ◽

2015 ◽

Vol 7 ◽

pp. e2015003 ◽

Cited By ~ 9

Author(s):

Grzegorz Helbig ◽

Grazyna Bober ◽

Marek Seweryn ◽

Ryszard Wichary ◽

Andrzej Tukiendorf ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Disease Free Survival ◽

Interferon Α ◽

Secondary Malignancies ◽

Single Institution ◽

Chi Squared ◽

Disseminated Disease

Introduction. Imatinib mesylate (IM) remains a treatment of choice for chronic myeloid leukemia (CML) showing a remarkable efficacy and providing a perspective for a long disease-free survival. Due to the long-term administration of IM, the questions about the possible impact on the development of secondary malignancies (SM) are raised.Objective. To investigate the frequency and clinical outcome of secondary malignancies during IM therapy for CML.Material and Methods. The records of 221 CML patients treated with IM between 2003-2013 in single institution were reviewed. The Chi-squared test was used for statistic analysis.Results. Secondary malignancies developed in eight out of the 221 patients (3.6%) receiving IM for a median of 61 months (range, 10-137 months). Female/male ratio was 5/3. Two patients were diagnosed with their CML at accelerated phase whereas 6 had chronic phase. The median age at IM initiation was 58 years (range, 31-72 years). Five of these 8 SM patients received IM after other treatments failure: interferon α (n=5), hydroxyurea (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy. All patients were on IM at 400mg daily at SM occurrence. The therapy for SM included surgery (n=3); chemotherapy only (n=3); and chemotherapy followed by radiotherapy (n=1). One patient did not receive treatment due to disseminated disease. At the time of SM development all patients were in hematologic and cytogenetic remission (CCR) of their CML and all patients continued their IM while receiving treatment for their SM. Among 8 patients with SM, five patients are alive and remain in CCR on IM whereas 3 patients died due to SM. The observed incidence of SM was found to be comparable with that expected in the age-adjusted population (chi-squared=0.4; p=0.52).Conclusions. The association between IM therapy for CML and SM development has not been found.

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A Retrospective Survey of Imatinib Mesylate Treatment for Chronic Myeloid Leukemia in a Northern France Region.

Blood ◽

10.1182/blood.v108.11.4800.4800 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4800-4800

Author(s):

Selim Corm ◽

Ariane Leroyer ◽

Mathieu Wemeau ◽

Bruno Bregman ◽

Abderrahim Oukessou ◽

...

Keyword(s):

Survival Rate ◽

Chronic Myeloid Leukemia ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

Real Life ◽

Chronic Phase ◽

Disease Stage ◽

Northern France ◽

Advanced Phase

Abstract Objective: To describe the use and results of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) in the Nord-Pas de Calais Region in Northern France (~ 4 millions inhabitants). Methods: we identified all IM treated patients (pts) within the population of all confirmed diagnosis of CML occurred during the period 1985–2004. IM resistance (haematological and cytogenetic imatinib failure and suboptimal response) was evaluated according to the European LeukemiaNet consensus. Results: 302 pts (38.6% of the global cohort of diagnosis) were included in this retrospective study. If we consider new diagnosis occurred after Januar 1st 2001, 163 pts (90.6%) have been treated by IM. At the initiation of IM: 18 pts (6%) were in advanced phase (accelerated and blastic), 245 pts (81,1%) in chronic phase (CP) (with Ph+ metaphases > 35%), 35 (11,6%) had major cytogenetic response (MCyR) obtained with interferon (IFN) or bone marrow transplantation (BMT). Four pts (1,3%) had an unknown status. The percentage of alive pts at the last update (December 31th 2005) according to the disease stage at initiation of treatment is given in the table 1.In the sample of 245 CP pts, 139 (56.7%) had been previously treated by IFN, the median CML duration prior to IM was 4.7 months [0–174], the median IM treatment duration was 31.3 months [0.5–72.3] and the median follow-up after IM initiation was 36 month [5.2–72.3]. 214 pts (87.30%) were alive at the last update with 169 (79%) still on IM and 161 (75.2%) on IM as monotherapy. The median and mean IM daily doses of alive pts are 400 mg and 409.5 mg, respectively. Seventeen pts (6.9%) stopped IM for intolerance. The haematological and cytogenetic follow-up was informative for 206 CP pts (84.1%): MCyR 155 pts (75.2%) and CCyR 144 pts (69.9%). IM resistance occurred in 73 (35.4%) of these 206 evaluable pts, including 23 (11.1%) accelerations and blastic transformations. In the subgroup of IM resistant pts 47 (64.4%) have increased their IM posology. The mean of the maximum daily dose in the resistant subgroup was 607.5 mg (median 600 mg). BCR-ABL kinase domain mutations were found in 15 (20.5%) pts amoung IM resistant population. The estimated 5-years survival rate of the CP pts is 81.3%. Previous treatment by IFN doesn’t influence significantly the survival, nor the duration of the disease before IM initiation, even if we found a trend for a better survival when this period was inferior to 6 months (5 years survival rate 90.4% vs 77.5%, p=0.16). BMT was performed for 31 pts (10.3%) including 19 pts (6.3%) after the initiation of IM therapy. Conclusion: these real life observations show the large use of IM in the last years and its great impact on the management and the survival of CML pts. IM resistance occurs in 1/3 of pts but the disease duration prior to IM is heterogeneous. An increase of IM dose has been tried in most IM resistant pts. The response to the different therapy adaptations is under study and will be presented. The vast majority of pts are still on IM therapy at the last update. Table 1

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Cost-Effectiveness Analysis for Integral Treatment of Chronic Myeloid Leukemia in Chronic Phase at the Instituto Mexicano del Seguro Social (IMSS) Mexico.

Blood ◽

10.1182/blood.v108.11.4789.4789 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4789-4789

Author(s):

Luisa Tenorio ◽

Juan Vargas E ◽

Enrique Baez ◽

Carolina Afanador ◽

Leon Zapata ◽

...

Keyword(s):

Cost Effectiveness ◽

Chronic Myeloid Leukemia ◽

Medical Care ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Number Of Patients ◽

Health Institutions ◽

Clinical Records ◽

The Cost

Abstract The economic analysis has become a priority for health institutions as a result of the increase in medical care costs. Therefore, an analysis model was developed integrating clinical and economic outcomes for the Medical care of chronic myeloid leukemia (CML) in chronic pahse. Objective: To perform a cost-effectiveness assessment of the therapeutic alternatives for CML at UMAE No.25 IMSS. Methodology: Economic evaluation of the use of imatinib mesylate (IM) vs. interferon + citarabine (INF/AraC), using as an effectiveness indicator, the number needed for treatment (NNT), to achieve a complete cytogenetic response (CCR) at 24 and 30 months was used. The integral care was obtained from the revision of clinical records in the UMAE 25, and from disease related-costs published by the IMSS. Results: The NNT reveals the amount of patients that need to be treated with one or the other of the therapies to obtain the desired result (CCR), which means that for every 1.15 patients IC 95% (1.06–1.25) treated with IM for 24 months, one will reach the CCR, with a cost of $867,729 mexican pesos (mx), in comparison to the care cost for 7.14 patients IC 95 % (5.75–8.88) patients that are required to be treated with IFN/AraC for 24 months to obtain the same result, with a cost of mx $4,454,565. This difference is higher when results are assessed at 30 months: A cost of NNT care of 1.27 patients IC 95% (1.07–1.50) of mx $1,178,848 for IM vs. mx $10,182,116 for NNT care of the 13.5 patients, CI 95% (9.40–19.43) required to achieve a CCR with IFN/AraC. Discussion: Comparing these results with the cost of the main treatment used during the same time, the expense effectiveness is evident. In other words, for each peso spent on IM at 24 months, mx $0.63 are effective, whilst for each peso spent on IFN/AraC, only mx $0.02 are beneficial for the patient. When this same reasoning is applied to the success cost at 30 months, we see that for each peso spent on IM, $0.58 are effective vs mx $0.01 per peso effectiveness spent on IFN/AraC. Conclusions: The superiority of IM is evident compared to INF/AraC in regards to the effectiveness of achieving CCR at 24 and 30 months. This positive difference in favor of imatinib mesylate is reflected on the cost that Health Institutions have to spend, in order to obtain a successful CCR, due to the decreased number of patients necessary to treat with IM, in order to achieve this success.

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