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Drug-to-drug interactions of tyrosine kinase inhibitors in chronic myeloid leukemia patients. Is it a real problem?

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Abstract

With tyrosine kinase inhibitors (TKI), chronic myeloid leukemia (CML) patients are achieving similar rates of survival to the general population and some treatment aspects such as adherence and drug-to-drug interactions (DDI) are becoming increasingly important. Our aim was to investigate the frequency and real clinical consequences of DDI between TKI and concurrent medications in CML. We performed a retrospective multicenter study including 105 patients receiving 134 TKI treatments. Sixty-three patients (60%) had at least one potential DDI. The mean number of concomitant medications was 4.8 (0–19). The mean number of DDI by TKI treatment was 1.2 (0–8); it increased with the number of concomitant medications and age in a significant manner. A total of 159 DDI were detected, involving 55 different drugs. The most common drug classes involved were proton pump inhibitors, statins, and antidepressants. A DDI-related clinical effect (toxicity and/or lack of efficacy) was suspected during the common course of patient follow-up in only five patients (4.7%). This number increased to 20% when data were centrally reviewed. Most of the adverse events (AE) attributed to DDIs were mild. The most common were diarrhea, vomiting, edema, cramps, and transaminitis. Nilotinib and dasatinib showed a tendency towards a higher risk of DDI compared with imatinib. There were no significant differences in AE frequency or in treatment response between patients with or without DDI. Due to their frequency, and their potential to cause clinically relevant effects, DDI are an important aspect of CML management.

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Author information

Authors and Affiliations

  1. Servicio de Hematología, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Santiago Osorio & Ignacio Gómez-Centurión

  2. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain

    Santiago Osorio, Vicente Escudero-Vilaplana, Ignacio Gómez-Centurión & Xandra Garcia-Gonzalez

  3. Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Vicente Escudero-Vilaplana & Xandra Garcia-Gonzalez

  4. Servicio de Hematología, Hospital Universitario Clínico Virgen de la Arrixaca, Murcia, Spain

    Raúl Pérez-López

  5. Servicio de Hematología, Hospital Universitario 12 de Octubre, Madrid, Spain

    Rosa Ayala

  6. Servicio de Hematología, Hospital Universitari Mútua Terrassa, Terrassa, Spain

    Ferrán Vall-Llovera

  7. Servicio de Hematología, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Valentín García-Gutierrez

  8. Servicio de Hematología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain

    María Teresa Gómez Casares & María Nieves Sáez Perdomo

  9. Servicio de Hematología, Complejo Hospitalario Universitario Insular Materno Infantil de Canarias, Las Palmas de Gran Canaria, Spain

    José David González San Miguel

  10. Servicio de Hematología, Hospital Universitario Infanta Leonor, Madrid, Spain

    José-Ángel Hernández-Rivas

  11. Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain

    Fermín Sánchez-Guijo

  12. Servicio de Hematología, Hospital General Universitario Santa Lucía, Cartagena, Murcia, Spain

    Ana Belén Martínez-García

  13. Servicio de Hematología, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain

    Lucia Villalón

  14. Servicio de Hematología, Hospital General Universitario de Elche, Elche, Alicante, Spain

    Venancio Conesa-García

  15. Servicio de Hematología, Hospital Universitario Virgen Macarena, Sevilla, Spain

    Alicia Rodriguez & Úrsula Baños

  16. Servicio de Hematología, Hospital Virgen de la Salud, Toledo, Spain

    Felipe Casado

  17. Servicio de Hematología, Hospital Universitario de la Princesa, Madrid, Spain

    Juan Luis Steegmann

Authors
  1. Santiago Osorio
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  2. Vicente Escudero-Vilaplana
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  3. Ignacio Gómez-Centurión
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  4. Raúl Pérez-López
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  5. Rosa Ayala
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  6. Ferrán Vall-Llovera
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  7. Valentín García-Gutierrez
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  8. María Teresa Gómez Casares
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  9. José David González San Miguel
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  10. José-Ángel Hernández-Rivas
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  11. Fermín Sánchez-Guijo
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  12. Ana Belén Martínez-García
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  13. Lucia Villalón
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  14. Venancio Conesa-García
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  15. Alicia Rodriguez
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  16. Felipe Casado
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  17. Xandra Garcia-Gonzalez
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  18. María Nieves Sáez Perdomo
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  19. Úrsula Baños
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  20. Juan Luis Steegmann
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Consortia

On behalf of the CML Spanish Group (GELMC)

Corresponding author

Correspondence to Santiago Osorio.

Ethics declarations

This collaborative study was performed in 15 centers within the framework of the Spanish CML Group. It was approved by the Spanish Drug Agency, and the institutional Research Ethics Committees. All procedures followed were in accordance with the ethical standards of these national and institutional Committees, and with the Helsinki Declaration of 1975, as revised in 2008. Due to the retrospective nature of the study, with no interventions, formal informed consent was not considered necessary by the aforementioned Committees for approval.

Conflict of interest

The authors declare that they have no conflict of interest.

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Osorio, S., Escudero-Vilaplana, V., Gómez-Centurión, I. et al. Drug-to-drug interactions of tyrosine kinase inhibitors in chronic myeloid leukemia patients. Is it a real problem?. Ann Hematol 97, 2089–2098 (2018). https://doi.org/10.1007/s00277-018-3413-7

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  • DOI: https://doi.org/10.1007/s00277-018-3413-7

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