Comparison of effectiveness and safety of Iranian-made vs. Indian-made imatinib in treatment of chronic myeloid leukemia (original) (raw)
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Annals of Hematology
In India, CML is the commonest adult leukemia. Imatinib is the gold standard for frontline treatment of newly diagnosed CML-CP patients. The present study was conducted to assess the efficacy and safety of generic imatinib in newly diagnosed CML-CP patients. In this prospective study, 76 newly diagnosed CML-CP patients received generic imatinib. They were monitored as per the ELN2013 recommendation. Karyotyping and BCR-ABL transcript level were done at specified time points. Adverse effects, if any, were documented as per the NCI-CTCAE criteria v4.03. Statistical analysis was done using standard methods. A total of 76 patients included in the study; median age was 36 years. The most common (71%) presenting symptom was fatigue; splenomegaly was found in all patients. CHR was achieved in 97% cases. At 3 months, 64.5% patients achieved ERM. At 6 months, CCyR and MCyR had seen in 65% and 68% cases, respectively. MMR achieved at 12 months in 44% cases. Most common hematological and non-hematological toxicity were anemia and skin changes seen in 89.5% and 71% cases, respectively. With generic imatinib therapy, the results of treatment outcome and safety profile were comparable with original imatinib. The added advantage was gross reduction in cost of therapy meeting unmet needs in CML patients in countries with resource constraints.
Treatment of chronic myeloid leukemia in the imatinib era
Cancer, 2007
BACKGROUND. There is paucity of data from developing countries on the efficacy and safety of imatinib mesylate in chronic myeloid leukemia (CML). The primary objective of this study was to document complete and partial cytogenetic responses to imatinib in all phases of CML. Secondary objectives included evaluations of complete hematologic response, safety, time to progression, and survival. METHODS. Two hundred seventy-five patients in all phases of CML who received treatment with imatinib from January 2001 to December 2005 were included in the study. All patients had either Philadelphia chromosome (Ph) on bone marrow or BCR-ABL positive in peripheral blood by polymerase chain reaction. RESULTS. After a median follow-up of 18 months, major cytogenetic responses (Ph < 35%) in chronic phase (CP), accelerated phase (AP), and blastic phase (BP) were documented in 61%, 57%, and 28% of patients, respectively. A complete cytogenetic response was observed in 39.4%, 35.7%, and 14.3% of patients in CP, AP, and BP, respectively; and a complete hematologic response was observed in 90%, 86%, and 30%, respectively. The median time to progression at 18 months was 91% in CP and 68% in AP. The overall survivals in CP, AP, and BP at 18 months was 92%, 74%, and 38%, respectively. CONCLUSIONS. Impressive hematologic, cytogenetic, and molecular responses to imatinib were observed, similar to the responses reported in patients from Western countries. Patients had good compliance, toxicity was limited, and overall quality of life was improved markedly. The results indicated that the biology of CML is not different in patients from developing countries.
Vojnosanitetski pregled
Background / Aim. The treatment of chronic myeloid leukemia (CML) has changed dramatically with the advent of targeted therapies. The study aimed to assess the efficacy of generic imatinib in CML patients treated in our center. Methods The study was retrospective. It included 101 patients with the diagnosis of CMLchronic phase (CP). There were two study groups. Group 1 included 55 patients initially treated with branded imatinib and then switched to generic imatinib. Group 2 consisted of 46 newly diagnosed patients who received only generic imatinib from the start of therapy. Results. The patients were treated with branded imatinib for the mean of 42 months (range 6-132 months) before switching to generic imatinib. Treatment with generic imatinib lasted for 25 months in average (range 3-66 months). A quarter of the patients from Group 1 lost their cytogenetic response after being switched to generic imatinib but without signs of transformation to acute leukemia. Patients treated with branded imatinib had a significantly longer event-free survival (EFS) and failure-free survival (FFS) (log-rank p=0.01 and p=0.03). These results could have been influenced by frequent changes of the brand and dosage formulation of generic imatinib. Conclusions. Our study showed a significantly longer EFS nad FFS on treatment with initially branded imatinib due to cross over study design, but provide some informative data of these two group of patients Key words: branded imatinib mesylate; generic imatinib mesylate; chronic myeloid leukemia. Apstrakt Uvod / Cilj. Ciljna terapija je značajno izmenila uspeh lečenje bolesnika sa hroničnom mijeloidnom leukemijom. Cilj rada je bio da se proceni efikasnost lečenja obolelih od hronične mijeloidne leukemije generičkim imatinibom u našem centru. Metode: Istraživanje je bilo retrospektivno. Obuhvatilo je 101 obolelog od hronične mijeloidne leukemije u hroničnj fazi. Bolesnici su bili podeljeni u dve grupe. Prvu grupu je činilo 55 bolesnika koji su inicijalno lečenji originalnim imatinibom i koji su kasnije tokom lečenja prevedeni na terapiju gneričkim imatinibom. Drugu grupu je činilo 46 novodijagnostikovanih bolesnika koji su od početka lečeni generičkim imatinibom. Rezultati. Bolesnici su originalnim imatinibom lečeni u proseku 42 meseca (od 6 do 132 4 meseca) nakon čega su prevedeni na generički imatinib. Lečenje generičkim imatinibom je u proseku trajalo 25 meseci (od 3 do 66 meseci). Četvrtina bolesnika prve grupe je izgubila citogenetski odgovor nakon prevoĎenja na generički imatinib. Nije bilo znakova za transformaciju u akutnu leukemiju. Bolesnici lečeni originalnim imatinibom su imali statistički značajno duže preživljavanje bez dogaĎaja koje podrazumeva smrtni ishod i preživljavanje bez neuspeha terapije (log-rank p=0.01 and p=0.03). Na ovakve rezultate je mogla imati uticaj učestala promena dozne formulacije i poizvoĎača generičkog imatiniba. Zaključak. Naše istraživanje je ukazalo na značajno duže preživljavanje bez dogaĎaja koje podrazumeva smrtni ishod i preživljavanje bez neuspeha terapije kod bolesnika koji su lečenje započeli originalnim imatinibom u odnosu na drugu grupu pacijenata koji su lečeni sve vreme generičkim imatinibom. Navedeni rezultati pružaju korisnu informaciju, ali se moraju tumačiti u kontekstu studije po tipu "cross over dizajna". Ključne reči: brendirani imatinib mesilat; generički imatinib mesilat; hronična mijeloidna leukemija.
Journal of Research in Pharmacy Practice, 2013
Objective: Chronic myeloid leukemia (CML) is a clonal hematopoietic disorder caused by acquired genetic defect in pluripotent stem cells characterized by acquisition of the philadelphia chromosome. The aim of this study was to compare the efficacy, safety and quality of life (QoL) in CML patients treated with imatinib or hydroxyurea. Methods: A prospective observational study was conducted on 40 patients with pathologically confirmed CML in an in-patient department of Mahavir Cancer Sansthan and Research Centre (tertiary care cancer hospital) in India. Patients were divided into two groups (group A: Imatinib consuming patients and group B: Hydroxyurea consuming patients). Complete blood count was done every month to assess the efficacy and safety/toxicity profile of these drugs. The results were analyzed 12 months after completion of treatment. QoL was assessed by The European Organization for Research and Treatment of Cancer QoL Questionnaire core 30. Hematological response was analyzed using kaplan-meier survival analysis. Chi-square test was applied to assess the association of two regimens with complete hematological response, hematological and non-hematological toxicity. White blood cell (WBC) was noted each month in every patient of each group and analyzed by generalized linear mode (repeated measures) analysis of variance (ANOVA). Independent t-test was used to compare changes in QoL between treatment groups. Findings: At the end of treatment, significant improvement (P = 0.001) in hematological response was observed in the group A (95%) compared to group B (30%). WBC count analyzed at each month of treatment by ANOVA achieved better results for patients treated with imatinib (P = 0.0001). The hematological toxicity was higher in imatinib group while non-hematological toxicity was higher in the hydroxyurea group; however only little toxicities such as nausea and constipation were statistically significant. QoL assessment of patients related to functional scale showed significantly better results in group A (P = 0.046). Conclusion: The study showed that imatinib has better profile compared to hydroxyurea, with siginificant statistical differences in terms of efficacy, non-hematological toxicity and QoL in CML patients. Even with such better efficacy and safety profile, pharmacoeconomic evaluation needs to be done to justify and support the use of imatinib for CML patients in India.
Hematologic and molecular responses to generic imatinib in patients with chronic myeloid leukemia
Chronic myeloid leukemia (CML), with an annual incidence of 1.6 cases per 100,000 adults, is the first malignancy that has a specific chromosomal abnormality uniquely linked to it. 1 It is associated with a characteristic chromosomal translocation called the Philadelphia chromosome (Ph). 2,3 This abnormally short chromosome is the result of a reciprocal translocation between the long arms of chromosomes 9 and 22, which generates the BCR-ABL fusion oncogene. 4,5 The BCR-ABL p210 fusion protein is found in more than 95% of patients with CML. 6 This oncoprotein is an activated tyrosine kinase stimulating several pathways transducing intercellular signals leading to abnormal cellular adhesion, enhanced proliferation, and inhibition of apoptosis. 7,8 Eradication of all cells containing BCR-ABL fusion transcript is accompanied by long-term, non-neoplastic, and non-clonal erythropoiesis and is a suitable option to cure these patients. 9 In recent years, numerous researchers aimed to destroy these cells, 10 and with the development of molecular techniques in 1998, the first generation of tyrosine kinase inhibitors called Imatinib mesylate was approved by the Food and Drug Administration. 11 Imatinib was specifically designed to bind adenosine triphosphate (ATP), the docking site of ABL-tyrosine kinase in the BCR-ABL oncoprotein, to inhibit its enzymatic activity, inactivate it, 12,13 and promote apoptosis in cells carrying this oncoprotein. 9 Imatib is the brand name for Imatinib mesylate, manufactured by the generic producer Cipla Limited (Mumbai, India) and is used in approximately 95% of CML patients in Iran due to its cheaper price (about 12 times cheaper) compared with the other available brand (Novartis, Basel, Switzerland). In this study, hematologic and molecular responses were evaluated in Iranian CML patients who received Imatib as the first-line therapy in the chronic phase of CML. Also, the correlation of these responses to the patient's age and sex, dosage, and duration of Imatib consumption was studied. Materials and Methods Study Group and Therapy Thirty chronic phase CML patients were selected from
The Turkish Journal of Hematology, 2013
Objective: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML). During therapy, a few patients may develop hematological and non-hematological adverse effects. Materials and Methods: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. Results: Two hundred CML patients in chronic phase were included in this study; the male:female ratio was 0.7:1 with mean age 39.06±13.21 years (ranged from 15-81 years). The study showed that the commonest hematological side effects were grade 2 anemia (12.5%) followed by leukopenia (8%) and thrombocytopenia (4%), while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%), followed by musculoskeletal pain (35.5%), then gastro-intestinal symptoms (vomiting, diarrhea) (19%). Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. Conclusion: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.
Clinical Lymphoma Myeloma and Leukemia, 2019
Context: Outcomes in patients with CML-BP are historically dismal. The median survival in patients with blastic phase CML is less than 12 months. Pathobiology of CML-BP involves various pathways with genetic and epigenetic abnormalities involved in transformation but isn't fully understood. These statements are applicable for CML with primary blast crisis (De-Novo CML BP). But some clinical data suggests that De-Novo CML-BP may have different pathobiology and prognosis for these patients may be better. Meanwhile, the distinction between De-Novo CML BP and De-Novo BCR-ABL (+) AML is challenging in many cases. Objective: The aim of this study is to describe the characteristics of patients with De-Novo CML-BP in Armenia. Design and Patients: Descriptive study of retrospective case series. This study involves patients who were diagnosed with CML in Hematology Center between 2014 and 2018. Distinction between Ph(+) AML and De-Novo CML-BP was based on splenomegaly, basophilia, Ph(+) metaphase proportion, left shift in myelogram. Results: Total 6 patients were identified, who were diagnosed with De-Novo CML-BP in the mentioned period of time. 4/6 of patients were males, 2/6 females. Median age at diagnosis was 48.5 years. Proportion of De-Novo CML-BP in total CML patients was 5.6%. Proportion in total CML-BP was 26%. 4/6 patients are still alive, median OS was not reached. 1 year OS was 66% (significantly better than in secondary CML-BP patients). 1 patient with concomitant 11q23 rearrangement received two cycles of standard 7+3 chemotherapy and imatinib 600 mg QID, he achieved MMR at 1 mo. Other 3 patients are in chronic phase now. 1 patient was treated with imatinib 600 mg alone and is in CP now. 2 other patients received imatinib 400 mg QID. The first patient who passed away initially was treated with imatinib 600 mg, after lack of effect he received Nilotinib 400 mg BID and passed away while he was in this treatment. The second patient passed away on imatinib 400 mg. No one of patients underwent Allo-HSCT because this procedure still isn't available in Armenia. Conclusions: Prognosis of CML with Primary Blast crisis with first and second generation TKIs not as effective as for CML-CP patients. Despite this, experience from Armenia reinforces the hypothesis that CML with primary blast crisis has different features and better prognosis from secondary CML-BP.
The Journal of the Association of Physicians of India
To evaluate the response of imatinib mesylate in chronic phase of chronic myeloid leukemia and to observe the significance of Sokal score and various factors which predict the response. This was a descriptive, prospective study conducted from May 2001 to September 2006. One hundred and thirty six patients with diagnosis of chronic myeloid leukemia in chronic phase were analyzed. Hematologic and cytogenetic responses were assessed according to defined criteria. The median age at time of diagnosis was 33 years (range, 12-65 years). Among them 86 were males, 50 were females. At the end of study response was analyzed overall and according to Sokal score. At median follow-up of 18 months, 122 patients were evaluable for cytogenetic response. Complete hematologic response was seen 86% while complete and major cytogenetic response was observed in 34.4% and 49.2% cases respectively. Analysis of variables like younger age, disease duration at time of starting imatinib failed to show any sign...
Indian Journal of Medical and Paediatric Oncology, 2013
The data presents 75 chronic myeloid leukemia patients diagnosed over a period 6 years i.e. from 2002 to 2008. The most common presentation was splenomegaly and 97% achieved complete hematological response at median duration of 4.3 weeks. The uniqueness of this study is follow-up with molecular response monitoring. Nearly, 30% patients achieved major molecular response (MMoR) by 12 months. 70% of patients achieved MMoR by median time of 60 months. Only 10% of the patient who achieved MMoR by 18 months had lost their responses subsequently.