Chronic Myeloid Leukemia Patient's Voice About the Experience of Treatment-Free Remission Failure: Results From the Italian Sub-Study of ENESTPath Exploring the Emotional Experience of Patients During Different Phases of a Clinical Trial.

Lidia Borghi,Massimiliano Bonifacio,Alessandra Iurlo,Antonio Cuneo,Francesca Lunghi,Claudia Baratè,Claudia Minotto,Giovanna Rege-Cambrin,Jens Haenig,Elena Vegni,Ester Maria Orlandi,Franca Falzetti,Enrico Capochiani,Sara Galimberti,Sharon Supekar,Simona Sica

doi:10.3389/fpsyg.2019.00329

Abstract

Background: The main objective of this study is to gain further insights on how chronic myeloid leukemia (CML) patients involved in an interventional clinical trial with the purpose of reaching treatment free remission (TFR) phase, perceived and experienced TFR failure. TFR failure was defined for the individual patient as either not being eligible for drug discontinuation or as having relapse in the TFR phase with reintroduction of nilotinib treatment.Methods: Using a qualitative approach, out of 25 patients with CML who experienced TFR failure 14 were interviewed. Patients’ views and experiences were explored using in-depth interviews, analyzed using the Interpretative Phenomenological Analysis (IPA).Results: The analysis of the interviews revealed that the experience of the diagnosis seems to have been lived as a traumatic break that has created a dichotomy, like an ambivalence in the ways in which CML patients perceived and experienced the whole disease journey, with contradictory feelings of both positive and negative emotions (e.g., a diagnosis of cancer, that is something distressing and of being afraid of, but also with a treatment and a life expectancies of which being grateful). This ambivalence of feelings was found to give meaning to the way in which patients cognitively and emotionally experienced the different steps of their disease history. Thus, four main issues, corresponding to different steps of the patients’ journey, were identified: (1) the moment of the diagnosis, (2) the experience of the illness journey: disease and treatment, (3) the moment of “TFR failure,” and (4) the impact of disease, treatment and relapse on the patient’s life.Conclusion: This qualitative analysis helps in understanding patients’ perspective, both in terms of getting access to the inner subjective experience of having CML and its strict relationship with the involvement in a trial or its cessation. Clinicians should consider that the way in which CML patients feel engaged in a clinical trial, create expectancies about TFR or experience the TFR failure is linked to the process of coping with the diagnosis, which is characterized by ambivalence.

Highlights

Chronic myeloid leukemia (CML) is a myeloid neoplasia characterized by the mutual translocation between chromosome 9 and 22 (Philadelphia chromosome) and by the BCR-ABL1 rearrangement, with a consequent synthesis of an uncontrolled tyrosine-kinase that induces increased proliferation, reduces apoptosis, and causes the entry of myeloid immature cells into the bloodstream (Rowley, 1973).In the last decades, thanks to the introduction of firstgeneration tyrosine kinase inhibitors (TKIs), the molecular-targeted therapy in CML became a reality, with the consequent improvement of the outcome for more than 90% of cases
As recently published data suggest that the duration of deep molecular response (DMR) (Saussele et al, 2017) is important for maintaining treatment-free remission (TFR), the data derived from the ENESTPath trial will provide further insights
Available data is mostly derived from interventional clinical trials with only Nilotinib having clear guidance for the TFR eligibility and the discontinuation procedure in the officially, health authority approved Summary of Products Characteristics, thereby leaving the process of decision making about interruption to each physician-patient dyad

Summary

Introduction

Thanks to the introduction of firstgeneration tyrosine kinase inhibitors (TKIs) (imatinib), the molecular-targeted therapy in CML became a reality, with the consequent improvement of the outcome for more than 90% of cases. Notwithstanding imatinib already greatly improved overall survival and allowed patients to achieve high clinical response rates (Hanfstein et al, 2012), the introduction of second-generation TKIs (nilotinib and dasatinib) as first-line therapy allowed a higher percentage of patients to achieve deeper and faster molecular responses (MR). The main objective of this study is to gain further insights on how chronic myeloid leukemia (CML) patients involved in an interventional clinical trial with the purpose of reaching treatment free remission (TFR) phase, perceived and experienced TFR failure. TFR failure was defined for the individual patient as either not being eligible for drug discontinuation or as having relapse in the TFR phase with reintroduction of nilotinib treatment

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Discussion

Conclusion