Failure of copy Imatib (CIPLA, India) to maintain hematologic and cytogenetic responses in chronic myeloid leukemia in chronic phase

Abstract

A 50-year-old woman presented with CML-CP and was initially treated with branded imatinib (Glivec) 400 mg/day. She rapidly achieved a complete hematologic response (CHR), at which point she switched therapy to a copy version of imatinib (Imatib). She received 400 mg/day of Imatib for 3 months, during which time her platelet count decreased from 250 x 10(9) to 105 x 10(9)/L and her hemoglobin count fell from 12.8 to 11 g/dL. The patient's total leukocyte count rose rapidly from 4 x 10(9) to 70 x 10(9)/L, and the CHR was lost. At this point, therapy was switched back to Glivec at 400 mg/day, and the CHR was rapidly regained. Furthermore, the patient achieved a major cytogenetic response by 6 months after reintroduction of Glivec. This case report suggests a difference in clinical efficacy between the authorized form of imatinib (Glivec) and the copy version of the drug (Imatib). The exact reasons for the observed difference in clinical efficacy are unknown, but likely relate to the use of alternative polymorphic forms of the drug. Glivec can be obtained directly from the manufacturer (Novartis Pharmaceuticals) through a variety of patient access programs that should be fully explored when needed.

Comparative Study of the Anti-leukemic Effects of Imatinib Mesylate, Glivec™ Tablet and Its Generic Formulation, OHK9511

“…22) Several case reports demonstrate hematologic relapse after switching from Glivec to a generic IM. [23][24][25][26] By contrast, recent reports show that the efficacy and tolerability of generics were comparable with those of Glivec after switching. [27][28][29] In the former reports, [23][24][25][26] the measurement of plasma concentration of imatinib was not performed at before and after changing to generic drugs.…”

Generic Imatinib Mesylate is as Effective as Original Glivec in the Clinical Management of CML.

“…16 On the other hand, a One of the clinical limitation of the reports which suggest generic TKIs are inferior that these studies involve relatively small number of cases or they are just case reports. 18,19 Moreover, some of those studies were financially supported by pharmaceutical companies. 18,19,20 Furthermore it is also unclear whether the generic IM which was used in these studies was bioequivalent or not.…”

“…18,19 Moreover, some of those studies were financially supported by pharmaceutical companies. 18,19,20 Furthermore it is also unclear whether the generic IM which was used in these studies was bioequivalent or not. 21 Likewise, there are speculations about the different crystal forms of IM may affect its clinical efficacy.…”

The Three Year Follow-up of CML Patients Treated with First-line Generic and First-line Branded Imatinib in Bosnia and Herzegovina.

“…Studies conducted in Egypt, Morocco, Columbia and Iraq highlighted the increased toxicity of generic imatinib in comparison to the branded imatinib. [6][7][8][9][10] However, studies from Turkey, Canada, India, Bosnia and Herzegovina, and Iran showed that generic therapy is well tolerated in CML patients and that adverse effects are manageable with supportive care. [11][12][13][14][15] In this study, we compared clinical outcomes of patients who received first-line Glivec (Group 1) to patients who received first-line generic imatinib (Group 2) in Bosnia and Herzegovina after three years of therapy.…”