Original Article
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Blood Res 2020; 55(3):
Published online September 30, 2020
https://doi.org/10.5045/br.2020.2020130
© The Korean Society of Hematology
Use of generic imatinib as first-line treatment in patients with chronic myeloid leukemia (CML): the GIMS (Glivec to Imatinib Switch) study
Correspondence to : Carlo Gambacorti-Passerini, Ph.D.
Department of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900, Monza (MB), Italy
E-mail: carlo.gambacorti@unimib.it
#These authors contributed equally to this work.
This is an Open Access article distributed unAcute myeloid leukemia, New FDA approvalsder the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Generic formulations of imatinib mesylate have been introduced in Western Europe since 2017 to treat patients with chronic myeloid leukemia (CML). However, results on the safety and efficacy of generic formulations are contrasting. The aim of this study was to investigate the safety and efficacy of generic imatinib in CML patients treated in 12 Italian institutes.
Methods
This is an observational, retro-prospective analysis of patients with CML for whom the treatment was switched from brand to generic imatinib. We analyzed and compared the variation in quantitative PCR values before and after the switch, and the proportion of patients who maintained molecular response after changing from brand to generic imatinib. Adverse events (AEs) were also evaluated.
Results
Two hundred patients were enrolled. The median PCR value after the switch was reduced by 0.25 compared to the values before the switch. A significant difference was found between median PCR values before and after the switch in favor of generic imatinib (P=0.003). Molecular responses remained stable in 69.0%, improved in 25.5%, and worsened in 5.5% of patients. AEs were similar in the pre- and post-switch periods; however, a significant difference was found in favor of generic imatinib for muscular cramps (P<0.0001), periorbital edema (P=0.0028), edema of the limbs (P<0.0001), fatigue (P=0.0482), and diarrhea (P=0.0027).
Conclusion
Our data indicate that generic imatinib does not have deleterious effects on CML control and present an acceptable safety profile, similar or better than brand imatinib.
Keywords Imatinib, Generic, Chronic myeloid leukemia, Generic imatinib, BCR/ABL, Adverse events
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Original Article
Blood Res 2020; 55(3): 139-145
Published online September 30, 2020 https://doi.org/10.5045/br.2020.2020130
Copyright © The Korean Society of Hematology.
Use of generic imatinib as first-line treatment in patients with chronic myeloid leukemia (CML): the GIMS (Glivec to Imatinib Switch) study
Maria Gemelli1#, Elena Maria Elli2#, Chiara Elena3, Alessandra Iurlo4, Tamara Intermesoli5, Margherita Maffioli6, Ester Pungolino7, Maria Cristina Carraro8, Mariella D’Adda9, Francesca Lunghi10, Michela Anghileri11, Nicola Polverelli12, Marianna Rossi13, Mattia Bacciocchi14, Elisa Bono3, Cristina Bucelli4, Francesco Passamonti6, Laura Antolini15, Carlo Gambacorti-Passerini2,14
1Oncology Unit, San Gerardo Hospital, ASST-Monza, 2Hematology Division and Bone Marrow Unit, Ospedale San Gerardo, ASSTMonza, Monza, 3Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, 4Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, 5Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, 6Hematology Unit, Ospedale di Circolo, Varese, 7Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, 8Hematology and Transfusional Medicine Unit, ASST Fatebenefratelli Sacco, Milan, 9Department of Hematology, ASST Spedali Civili di Brescia, Brescia, 10Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, IRCCS Milano, 11Oncology Department, ASST Lecco, Lecco, 12Chair of Hematology, Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, ASST Spedali Civili di Brescia, Brescia, 13Department of Hematology, Cancer Center, IRCCS Humanitas Research Hospital/Humanitas University, Rozzano, 14Department of Medicine and Surgery, University of Milano-Bicocca, 15Center of Biostatistics for Clinical Epidemiology, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
Correspondence to:Carlo Gambacorti-Passerini, Ph.D.
Department of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900, Monza (MB), Italy
E-mail: carlo.gambacorti@unimib.it
#These authors contributed equally to this work.
This is an Open Access article distributed unAcute myeloid leukemia, New FDA approvalsder the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Generic formulations of imatinib mesylate have been introduced in Western Europe since 2017 to treat patients with chronic myeloid leukemia (CML). However, results on the safety and efficacy of generic formulations are contrasting. The aim of this study was to investigate the safety and efficacy of generic imatinib in CML patients treated in 12 Italian institutes.
Methods
This is an observational, retro-prospective analysis of patients with CML for whom the treatment was switched from brand to generic imatinib. We analyzed and compared the variation in quantitative PCR values before and after the switch, and the proportion of patients who maintained molecular response after changing from brand to generic imatinib. Adverse events (AEs) were also evaluated.
Results
Two hundred patients were enrolled. The median PCR value after the switch was reduced by 0.25 compared to the values before the switch. A significant difference was found between median PCR values before and after the switch in favor of generic imatinib (P=0.003). Molecular responses remained stable in 69.0%, improved in 25.5%, and worsened in 5.5% of patients. AEs were similar in the pre- and post-switch periods; however, a significant difference was found in favor of generic imatinib for muscular cramps (P<0.0001), periorbital edema (P=0.0028), edema of the limbs (P<0.0001), fatigue (P=0.0482), and diarrhea (P=0.0027).
Conclusion
Our data indicate that generic imatinib does not have deleterious effects on CML control and present an acceptable safety profile, similar or better than brand imatinib.
Keywords: Imatinib, Generic, Chronic myeloid leukemia, Generic imatinib, BCR/ABL, Adverse events
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Table 1 . Demographic of patients and treatment characteristics (N=200)..
N % Gender Male 119 59.5 Female 81 40.5 Mean Standard deviation (SD) Age at diagnosis (yr) 48.6 15.7 Treatment with Glivec (yr) 9.1 4.9 N % Generic type Accord 119 58.5 Teva 109 54.5 Sandoz 41 20.5 Mylan 1 0.5 Reddy 1 0.5 N % No. of generics used 1 156 78.0 2 19 9.5 3 25 12.5
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Table 2 . Adverse events (AEs) with frequencies >1%; absolute number and percentage of G3-G4 for each event pre- and post-switch..
Adverse event (N=200) Before switch After switch P Only after switch Patients with AE G3-G4 grading Patients with AE G3-G4 grading N % N % N % N % N % 21 Muscular cramps 77 38.5 1 1.3 42 21.0 2 4.8 <0.0001 14 7.0 20 Edema limbs 41 20.5 3 7.3 17 8.5 0 0.0 <0.0001 2 1.0 19 Diarrhea 38 19.0 1 2.6 20 10.0 2 10.0 0.0027 9 4.5 18 Periorbital edema 35 17.5 0 0.0 21 10.5 0 0.0 0.0028 4 2.0 17 Fatigue 33 16.5 1 3.0 22 11.0 1 4.5 0.0482 10 5.0 16 Arthralgia 22 11.0 0 0.0 21 10.5 0 0.0 0.8575 15 7.5 15 Cutaneous rash 18 9.0 0 0.0 6 3.0 0 0.0 0.0027 2 1.0 14 Myalgia 16 8.0 1 6.3 4 2.0 0 0.0 0.0027 2 1.0 13 Nausea 12 6.0 1 8.3 9 4.5 1 11.1 0.4669 7 3.5 12 Conjunctival hyperemia 12 6.0 1 8.3 7 3.5 0 0.0 0.2253 6 3.0 11 Creatinine increased 7 3.5 0 0.0 2 1.0 0 0.0 0.6547 2 1.0 10 Other skin and subcutaneous tissue disorders 7 3.5 1 14.3 6 3.0 1 16.7 0.0588 1 0.5 9 Dyspepsia 6 3.0 1 16.7 1 0.5 0 0.0 0.3173 3 1.5 8 Anemia 6 3.0 0 0.0 3 1.5 0 0.0 0.0588 1 0.5 7 Headache 5 2.5 0 0.0 4 2.0 2 50.0 0.7055 3 1.5 6 Increased transaminase levels 4 2.0 0 0.0 0 0.0 0 0.0 0.0455 0 0.0 5 Neutrophil count decreased 4 2.0 2 50.0 0 0.0 0 0.0 0.0455 0 0.0 4 Blurred vision 3 1.5 0 0.0 1 0.5 0 0.0 1.0000 1 0.5 3 Hypertension 3 1.5 0 0.0 3 1.5 0 0.0 0.1573 0 0.0 2 Paresthesia 3 1.5 0 0.0 1 0.5 0 0.0 0.3173 1 0.5 1 Lipase increased 1 0.5 0 0.0 3 1.5 0 0.0 0.1573 2 1.0
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