Skip to main content

Switch from branded to generic imatinib: impact on molecular responses and safety in chronic-phase chronic myeloid leukemia patients

Abstract

Since July 2017, different generic imatinib formulations have been introduced in Italy for the treatment of patients with chronic myeloid leukemia (CML). We analyzed 168 chronic phase CML patients treated with branded imatinib for a median of 12 years (range 1–16) at a single institution who switched to a single generic formulation in order to assess the safety and impact on molecular response. The Sokal risk was low/intermediate/high in 63%, 33%, and 4% of patients, respectively. The median duration of generic imatinib treatment was 19 months (range 4–22). Twenty-seven percent of patients were in MMR and 73% were in deep molecular responses (MR4–4.5) at the time of the switch. After 12 months of treatment with generic imatinib, 140 patients were evaluable for response: 23.6% and 76.4% were respectively in MMR and in deep molecular response. When the degree of response was compared with the best molecular response observed with branded imatinib, it was found that 84% of patients maintained the response previously achieved, 6% improved it, and 10% of patients had a molecular fluctuation from the previous deep molecular response to MMR. Only 1 patient lost the MMR and no patient switched to another TKI for inefficacy. In terms of safety, 20% of patients reported new or worsening side effects, but only 2 patients returned to branded imatinib for toxicity. Our data show that the switch to generic imatinib in patients who have been previously treated with branded imatinib appears to maintain efficacy, although a proportion of patients experience new or worsening side effects.

This is a preview of subscription content, access via your institution.

References

  1. Goldman J, Melo J (2001) Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344(14):1084–1086

    CAS  Article  Google Scholar 

  2. Druker B, Tamura S, Buchdunger E et al (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2(5):561–566

    CAS  Article  Google Scholar 

  3. Jabbour E, Kantarjian H (2018) Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol 93(3):442–459

    Article  Google Scholar 

  4. Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, Baccarani M, Deininger MW, Cervantes F, Fujihara S, Ortmann CE, Menssen HD, Kantarjian H, O'Brien SG, Druker BJ, IRIS Investigators (2017) Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med 376(10):917–927

    CAS  Article  Google Scholar 

  5. Dou X, Qin Y, Lai Y, Shi H, Huang X, Jiang Q (2019) Comparable efficacy and safety of Chinese generic imatinib and branded imatinib in patients with newly diagnosed chronic myeloid leukemia: a retrospective study. Blood 134(suppl 1):2940

    Article  Google Scholar 

  6. Bhatwadekar SS, Deshpande SV, Methan A, Shah P (2019) Efficacy and safety of generic imatinib compared to glivec in chronic phase-chronic myeloid leukemia-single center retrospective analysis. Blood 134(suppl 1):4162

    Article  Google Scholar 

  7. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saußele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R (2013) European Leukemia Net recommendations for the management of chronic myeloid leukemia: 2013. Blood 122:872–884

    CAS  Article  Google Scholar 

  8. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, Tso CY, Braun TJ, Clarkson BD, Cervantes F (1984) Prognostic discrimination in ‘good-risk’ chronic granulocytic leukemia. Blood 63:789–799

    CAS  Article  Google Scholar 

  9. Geelen IGP, Sandin F, Thielen N, Janssen JJWM, Hoogendoorn M, Visser O, Cornelissen JJ, Hoglund M, Westerweel PE (2018) Validation of the EUTOS long-term survival score in a recent independent cohort of “real world” CML patients. Leukemia 32:2299–2303

    Article  Google Scholar 

  10. O’Brien S, Radich JP, Abboud CN, Akhtari M, Altman JK, Berman E, DeAngelo DJ, Deininger M, Devine S, Fathi AT, Gotlib J, Jagasia M, Kropf P, Moore JO, Pallera A, Pinilla-Ibarz J, Reddy VVB, Shah NP, Smith BD, Snyder DS, Wetzler M, Gregory K, Sundar H (2013) National comprehensive cancer network. Clinical Practice Guidelines in Oncology. Chronic Myelogenous Leukemia, Version 1.2014. J Natl Compr Cancer Netw 11:1327–1340

    Article  Google Scholar 

  11. Cross NC, White HE, Colomer D et al (2015) Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia. Leukemia 29:999–1003

    CAS  Article  Google Scholar 

  12. Kaplan EL, Meyer P (1958) Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–465

  13. Bonifacio M, Scaffidi L, Binotto G et al (2018) Safety and efficacy of switching from branded to generic imatinib in chronic phase chronic myeloid leukemia patients treated in Italy. Leuk Res 74:75–79

    CAS  Article  Google Scholar 

  14. Eskazan AE, Ayer M, Kantarcioglu B, Arica D, Demirel N, Aydin D, Yalniz FF, Elverdi T, Salihoglu A, Ar MC, Ongoren Aydin S, Baslar Z, Aydin Y, Tuzuner N, Ozbek U, Soysal T (2014) First line treatment of chronic myeloid leukemia patients with the generic formulations of imatinib mesylate. Br J Haematol 167:139–141

    CAS  Article  Google Scholar 

  15. Awidi A, Abbasi S (2017 Dec) Alrabi K, et al Generic Imatinib Therapy Among Jordanians: An Observational Assessment of Efficacy and Safety in Routine Clinical Practice. Clin Lymphoma Myeloma Leuk 17:e55–e61

    Article  Google Scholar 

  16. Cojbasic I, Macukanovic-Golubovic L, Vucic M, Cojbasic Z (2019) Generic imatinib in chronic myeloid leukemia treatment: long-term follow-up. Clin Lymphoma Myeloma Leuk 19:e526–e531

    Article  Google Scholar 

  17. Lejniece S, Udre I, Rivkina A (2017) Generic imatinib in the treatment of chronic myeloid leukemia: two years’experience in Latvia. Exp Oncol 39:151–154

    CAS  Article  Google Scholar 

  18. Eskazan AE, Sadri S, Keskin D, Ayer M, Kantarcioglu B, Demirel N, Aydin D, Aydinli F, Yokus O, Ozunal IE, Berk S, Yalniz FF, Elverdi T, Salihoglu A, Ar MC, Ongoren S, Baslar Z, Aydin Y, Tuzuner N, Ozbek U, Soysal T (2017) Outcomes of chronic myeloid leukemia patients with early molecular response at 3 and 6 months: a comparative analysis of generic imatinib and glivec. Clin Lymphoma Myeloma Leuk 17:804–811

    Article  Google Scholar 

  19. Islamagic E, Hasic A, Kurtovic S, Suljovic Hadzimesic E, Mehinovic L, Kozaric M, Kurtovic-Kozaric A (2017) The efficacy of generic imatinib as first- and second-line therapy: 3-year follow-up of patients with chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk 17:238–240

    Article  Google Scholar 

  20. Sacha T, Gora-Tybor J, Szarejko M et al (2017) A multicentre prospective study on efficacy and safety of imatinib generics: a report from Polish Adult Leukemia Group imatinib generics registry. Am J Hematol 92:e125–e128

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

MB and ES wrote the manuscript and analyze data; GC and DD performed molecular analyses; RL, SP, FS and ADP followed patients and collected data; FE, MM, and RF revised the final version of the paper.

Corresponding author

Correspondence to Massimo Breccia.

Ethics declarations

Conflict of interests

MB received honoraria from Novartis, Pfizer, Incyte, Celgene. FE received personal fees from Amgen, BMS, Orsenix, Incyte and Takeda. Research grants (to his Institution) from Amgen, outside the submitted work. All the other authors have no conflict of interests

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the responsible institution and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this kind of study, formal consent is not required.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Scalzulli, E., Colafigli, G., Latagliata, R. et al. Switch from branded to generic imatinib: impact on molecular responses and safety in chronic-phase chronic myeloid leukemia patients. Ann Hematol 99, 2773–2777 (2020). https://doi.org/10.1007/s00277-020-04096-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-020-04096-1

Keywords

  • Chronic myeloid leukemia
  • Tyrosine-kinase inhibitor
  • Generic imatinib
  • Molecular response
  • Adverse events