Efficacy and safety of generic imatinib after switching from original imatinib in patients treated for chronic myeloid leukemia in the United States

Iman Abou Dalle, Hagop Kantarjian, Jan Burger, Zeev Estrov, Maro Ohanian, Srdan Verstovsek, Farhad Ravandi, Gautam Borthakur, Guillermo Garcia-Manero, Elias Jabbour, Jorge Cortes, Iman Abou Dalle, Hagop Kantarjian, Jan Burger, Zeev Estrov, Maro Ohanian, Srdan Verstovsek, Farhad Ravandi, Gautam Borthakur, Guillermo Garcia-Manero, Elias Jabbour, Jorge Cortes

Abstract

Introduction: Imatinib is standard therapy for patients with chronic myeloid leukemia (CML). In February 2016, a generic formulation entered the US market. Physicians and patients are frequently concerned about whether switching from original to generic drugs may affect the efficacy and/or safety.

Materials and methods: This is an observational retrospective study using medical charts of patients diagnosed with CML in the chronic phase who were treated with original imatinib from the year 2000 to 2017 and who were subsequently switched to generic imatinib.

Results: In this study, 38 patients have switched to generic imatinib. Before the switch, responses were assessed on all patients, all of them were in CCyR and 36 (95%) were in MMR, including 28 (74%) with MR4.5. Patients have received generic imatinib for a median of 19.4 (range, 3.4-46.3) months. Molecular responses after switching were stable in 89%, improved in 8%, and worsened in 3% of patients. After switching, 15 (39%) patients reported new or worsening adverse events, including 5 (13%) patients with edema, 8 (21%) muscle cramps, 7 (18%) nausea, 6 (16%) diarrhea, and 5 (13%) fatigue.

Discussion: Bioequivalence studies demonstrated the same rate and extent of absorption of generic imatinib compared to the original form, which led to the FDA approval. In our observational series, most of the patients maintained their responses and none lost MMR. Adverse events noted were mild and well tolerated.

Conclusion: A change from original to generic imatinib appears to maintain efficacy and be generally safe. More patients and longer follow-up are required to confirm these observations.

Keywords: bioequivalence; generic; imatinib; leukemia; safety.

Conflict of interest statement

JC has research support from Ariad, Bristol‐Myers‐Squibb (BMS), Novartis, Pfizer, Sun Pharma, and Teva, and is a consultant for Ariad, BMS, Fusion Therapeutics, Pfizer, and Teva.

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Changes in BCR‐ABL1/ABL1 PCR at multiple time points before and after switching from original to generic imatinib. Only patients with detectable PCR at any time were included in this graph (N = 11). Among patients with undetectable PCR, 27/28 patients maintained MR4.5 after the switch after a median follow‐up of 20 mo

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