OUTCOME OF FRONTLINE TREATMENT WITH “GENERIC” IMATINIB IN ADULT PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN ALGERIAN POPULATION: A MULTICENTER STUDY
Main Article Content
Keywords
Chronic myeloid, leukemia
Abstract
Introduction:
In a developing country like Algeria, such expensive therapy is not available. Alternative approaches are needed to help these adult. In Algeria ‘imatib’ (CIPLA-India) was introduced in 2006; but no study has been published yet in the North Africa region regarding response and outcome of this copy in CML patients. The goal of this multicenter study is to characterize newly adult CML in the western region of Algeria and to assess the effectiveness and safety of imatib (IM, copy) as frontline therapy for patients with CML.
Patients and Methods:
The study was carried out in 7 hematology centers in the western Algeria. Patients, who were diagnosed to be suffering from CML between January 1st, 2007 and December 31st, 2014 were selected for data analysis. All patients received a copy preparation, consisting of the alpha crystal form of imatinib, (IM, copy) at a oral dose of 400 mg daily and monitored for tolerance and side effects while on therapy.
Results:
Between January 2007 and December 2014, 355 patients with CML were treated with imatib (Copy). The median follow- up of the study was 46 months (range: 13–107 months). Complete hematological response (CHR) was seen in 83% of patients within 3 months. According to the Sokal score, 72% patients with low, 78% with intermediate and 69% with high risk disease achieved a CHR in 3 months (p=0.26) and according to the EUTOS score, 81% of patients with low and 70% with high risk disease achieved a CHR in 3 months (p=0.08). The major molecular response (MMR) at six months (M6), M9, M12, M18 and M24 was 21%, 38%, 35%, 51% and 67% respectively and 34% of patients achieved a complete molecular response (CMR). The projected 5-year overall survival (OS) rate was 83%. Side effects of imatib (copy) in this study were similar to those reported previously for the entire imatinib mesylate treatment study and only 8% of patients were intolerant to imatib (copy) and treated with a second generation of BCR-ABL inhibitor.
Conclusion:
This study reflects real world experience treating patients with CML in a developing country and thus sheds light on differences in this population compared to Western countries. In conclusion, imatib (copy) is effective and safe in treating patients with CML in chronic phase and proves to have a durable outcome. To our knowledge this is the first study reporting the response to imatib (copy) in a Algerian population.
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References
[2] Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM: The biology of chronic myeloid leukemia. N Engl J Med 1999, 341:164-172.
[3] O’Brien SG, Guilhot F, Goldman JM, et al: International randomized study of interferon versus STI571 (IRIS) 7-year follow-up: sustained survival, low rate of transformation and increased rate of major molecular response (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM). Blood 2008; 112:76. ?
[4] Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010; 362:2251-9. ?
[5] O'Hare T, Shakespeare WX, Zhu X, et al. AP24534, a pan-BCR- ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 2009; 16 : 401-412.
[6] Cipla Imatib Product Website. Accessed November, 2008 at www.cipla.com.
[7] Gabert J, Beillard E, van der Velden VH, et al. Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia—a Europe Against Cancer program. Leukemia. 2003 ; 17: 2318–57.
[8] Baccarani M, Cortes J, Pane F, et al: Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009 [published online ahead of print November 2, 2009].
[9] BaccaraniMCalculation of relative risk of CML patients [online] 2010 [last changed 2010/11/08]. Available from: http://www.leukemia-net.org/ content/leukemias/cml/cml_score/.
[10] K Djouadi, N Abdennebi, F Harieche, R AhmedNacer, RM Hamladji, A Bouchakour, et al. Epidemiological approach of chronic myeloid leukemia. Algerian-tunisian study. Blood 2016 128:5440
[11] A. F. Fleming and C. Menendez, “Blood,” in Principles of Medicine in Africa, E. Parry, R. Godfrey, D. Mabey, and G. Gill, Eds., vol. 78, Cambridge University Press, Cambridge, UK, 2004.
[12] F. D. Groves, M. S. Linet, and S. S. Devesa, “Patterns of occurrence of the leukaemias,” European Journal of Cancer Part A, vol. 31, no. 6, pp. 941–949, 1995.
[13] C. C. Okany and O. O. Akinyanju, “Chronic leukaemia: an African experience,” Medical Oncology and Tumor Pharmacotherapy, vol. 6, no. 3, pp. 189–194, 1989.
[14] F. D. Groves, M. S. Linet, and S. S. Devesa, “Patterns of occurrence of the leukaemias,” European Journal of Cancer Part A, vol. 31, no. 6, pp. 941–949, 1995.
[15] O’Brien SG, Guilhot F, Goldman JM, et al: International randomized study of interferon versus STI571 (IRIS) 7-year follow-up: sustained survival, low rate of transformation and increased rate of major molecular response (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM). Blood 2008; 112: 76.
(16) De Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, Szydlo R, Olavarria E, Kaeda J, Goldman JM, Marin D. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008 Jul 10;26(20):3358-63.
[17] Hadi Alphonse Goubran. Failure of a non-authorized copy product to maintain response achieved with imatinib in a patient with chronic phase chronic myeloid leukemia: a case report. Journal of Medical Case Reports 2009, 3:7112
[18] Zoubir Chouffai. Hematologic Relapse after? 2 Years on a Non-Authorized Copy Version of Imatinib in a Patient with Chronic Myeloid Leukemia in Chronic Phase: A Case Report. Case Rep Oncol 2010; 3: 27
[19] Inas A Asfour and Shereen A Elshazly. Changing therapy from Glivec® to a "copy" imatinib results in a worsening of chronic myeloid leukemia disease status: two case reports. Cases Journal 2009, 2:9342
(20) Mattar M1. Failure of copy Imatib (CIPLA, India) to maintain hematologic and cytogenetic responses in chronic myeloid leukemia in chronic phase. Int J Hematol. 2010 Jan; 91(1):104-6.
(21) Ostojic A1, Sertic D2, Roncevic P2,Peric ZGranic PMatic et al. Comparison of Branded and Generic Imatinib Plasma Concentrations in Patients With Chronic Myelogenous Leukemia: Unicentric Study. Clin Lymphoma Myeloma Leuk. 2016 Aug;16(8):472-6.
(22) Jiang Q, Zhao D1, Jin J, Wu D, Meng F, Hu J, et al. A prospective, multi-centre clinical trial to evaluate the early clinical efficacy and safety of a generic imatinib in treating patients with chronic phase of chronic myelogenous leukemia. Zhonghua Xue Ye Xue Za Zhi. 2015 Aug;36(8):651-5.
[23] Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gatter- mann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA, IRIS Investigators: Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006, 355(23): 2408-2417.
[24] Matthew Kang, Anargyros Xenocostas, Alejandro Lazo-Langner, Ian H. Chin-Yee, Kang Howson-Jan, and Maisam Abouzeenni. Impact of Transition to Generic Imatinib in the Molecular Response Among Patients with Chronic Myeloid Leukemia, Blood 2014, vol.124: 5527.
[25] Jyotsna Kapoor, Narendra Agrawal, Rayaz Ahmed, Sanjeev Kumar Sharma, Anshul Gupta and Dinesh Bhurani. Factors Influencing Adherence to Imatinib in Indian Chronic Myeloid Leukemia Patients: A Cross-Sectional Study. Mediterr J Hematol Infect Dis 2015, 7(1): e2015013, DOI: http://dx.doi.org/10.4084/MJHID.2015.013
[26] K. G. Koffi, D. C. Nanho, E. N’dathz, P. Kouehion, R. Dissieka, A. Attia, et al. The Effect of Imatinib Mesylate for Newly Diagnosed Philadelphia Chromosome-Positive, Chronic-Phase Myeloid Leukemia in Sub-Saharan African Patients: The Experience of Côte d’Ivoire. Advances in Hematology? Volume 2010, Article ID 268921, 6
[27] Gyan K Kayastha, Padma Gurung, Paras K Acharya, & al. Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate); the first generation specific tyrosine kinase inhibitor. BMC Blood Disorders 2010, 10:8