CML-104: Efficacy of Generic Imatinib After Switching from Original in Treatment of Patients with Chronic Myeloid Leukemia in the Republic of North Macedonia - A Single-Center Experience

Abstract

Context Imatinib, selective tyrosine kinase inhibitor (TKI), revolutionized treatment of chronic myeloid leukemia (CML) and changed the natural history of the disease. In 2013, a generic formulation came into the Republic of North Macedonia's market and replaced the original formulation, Glivec. Objective The aim of the study is to determine whether the efficacy of the generic Imatinib is the same as the original Imatinib-Glivec in patients treated for chronic myeloid leukemia in North Macedonia in terms of hematological and molecular responses in CML. Design This is an observational retrospective study using medical charts of patients diagnosed with CML in the chronic phase who were previously successfully treated with original Imatinib and subsequently switched to generic Imatinib. The patients were treated with generic Imatinib from the year 2013 to 2020. Patients or other participants 30 patients have been switched from original to generic Imatinib. All of them were receiving Imatinib at a dose of 400 mg/ daily prior and after switching. 17 (56.6%) of all patients were male, 13 (44%) were female. 28 of the patients completed the study, 2 of the patients lost their molecular response and were switched to second-generation TKI-Nilotinib. Results 30 patients have been switched to generic imatinib. Before the switch, all of the patients were in complete hematologic response (CHR), and all of them were in MMR. Patients have received generic Imatinib for a median of 88 months. Molecular response (MR) was decided with BCR-ABL1 gene transcript ratio that is reported as International Scale (IS). Complete hematologic response was accepted as white blood cells < 10×109/L, basophils <5%, no myelocytes, promyelocytes, myeloblasts in the differential, platelet count < 450×109/L and non-palpable spleen. All of them maintained their hematologic response. Molecular responses after switching were stable in 83.3% (25), improved in 3.3% (1), and worsened in 13.3% (4). After switching, only 3.3% (1) reported anemia as a side effect and had not reported a new adverse event. Conclusions In our observational series, most of the patients maintained their molecular response. The change from original to generic Imatinib appears to maintain efficacy and maintained CHR and MMR. Imatinib, selective tyrosine kinase inhibitor (TKI), revolutionized treatment of chronic myeloid leukemia (CML) and changed the natural history of the disease. In 2013, a generic formulation came into the Republic of North Macedonia's market and replaced the original formulation, Glivec. The aim of the study is to determine whether the efficacy of the generic Imatinib is the same as the original Imatinib-Glivec in patients treated for chronic myeloid leukemia in North Macedonia in terms of hematological and molecular responses in CML. This is an observational retrospective study using medical charts of patients diagnosed with CML in the chronic phase who were previously successfully treated with original Imatinib and subsequently switched to generic Imatinib. The patients were treated with generic Imatinib from the year 2013 to 2020. 30 patients have been switched from original to generic Imatinib. All of them were receiving Imatinib at a dose of 400 mg/ daily prior and after switching. 17 (56.6%) of all patients were male, 13 (44%) were female. 28 of the patients completed the study, 2 of the patients lost their molecular response and were switched to second-generation TKI-Nilotinib. 30 patients have been switched to generic imatinib. Before the switch, all of the patients were in complete hematologic response (CHR), and all of them were in MMR. Patients have received generic Imatinib for a median of 88 months. Molecular response (MR) was decided with BCR-ABL1 gene transcript ratio that is reported as International Scale (IS). Complete hematologic response was accepted as white blood cells < 10×109/L, basophils <5%, no myelocytes, promyelocytes, myeloblasts in the differential, platelet count < 450×109/L and non-palpable spleen. All of them maintained their hematologic response. Molecular responses after switching were stable in 83.3% (25), improved in 3.3% (1), and worsened in 13.3% (4). After switching, only 3.3% (1) reported anemia as a side effect and had not reported a new adverse event. In our observational series, most of the patients maintained their molecular response. The change from original to generic Imatinib appears to maintain efficacy and maintained CHR and MMR.