Selected studies assessing PRO in CML patients
| Reference . | PRO instruments . | Main objective . | Summary of conclusions and clinical implications . |
|---|---|---|---|
| PROs in CP-CML patients treated with first-line imatinib | |||
| Hahn et al21 | FACT-BRM; EQ-5D | To compare the impact of QoL in CP-CML patients receiving imatinib or IFN-α plus low-dose cytarabine (IRIS study). Crossover to the other treatment arm is permitted due to a lack of efficacy or treatment intolerance. | QoL outcomes are better with imatinib than IFN-α plus low-dose cytarabine as first-line therapy of CP-CML. A significant improvement in QoL also occurs in patients who cross over from IFN-α plus low-dose cytarabine to imatinib. Physical function and well-being and social and family well-being are better among men than among women. |
| Efficace et al22 | SF-36 plus ad hoc 9-item symptom checklist | To investigate whether CP-CML patients in treatment with long-term therapy (at least 3 y) with first-line imatinib have a different QoL profile compared with the general population. | Patients aged ≥60 y have a QoL profile very similar to that reported by their respective peers (without cancer) in the general population. However, younger patients aged 18–59 y report clinically meaningful impairments in most aspects of QoL, in particular in role limitations because of physical and emotional problems. Women have a worse profile than men when each patient was compared with his or her peer in the general population. Fatigue is the most prevalent symptom. |
| Efficace et al23 | SF-36; FACIT-Fatigue; MSPSS | To investigate factors associated with long-term QoL outcomes of CP-CML patients in CCyR treated with imatinib therapy, and to investigate the relationships between fatigue and other treatment-related symptoms. | Fatigue is the main factor independently associated with long-term QoL of CML patients. Even small variation in fatigue severity corresponded to clinically meaningful impairments in overall QoL. Fatigue in this population does not occur by itself but clusters with other symptoms (mainly musculoskeletal pain and muscular cramps). |
| PROs in CML patients also treated with second-generation TKIs or in advanced phase (AP or BC) | |||
| Trask et al25 | FACT-Leu | To assess the impact of bosutinib treatment (until disease progression, unmanageable toxicity, or withdrawal of consent at the various time points) on the QoL of imatinib-resistant and imatinib-intolerant CP-CML patients. | CP-CML patients have little impairment in most aspects of QoL at the start of treatment. At baseline, there were no apparent differences in the FACT-Leu scales between imatinib-resistant and imatinib-intolerant CP-CML patients. Over the course of bosutinib therapy, only imatinib-intolerant CP-CML patients showed statistically significant and clinically meaningful improvements on several FACT-Leu scales. |
| Trask et al24 | FACT-Leu | To provide information on the QoL of CP-CML patients prior to first-line, second-line, and third-line therapy, and to provide the same information for those patients previously treated in the AP and BC of the disease. | CP-CML patients about to receive first-line treatment reported statistically significant (but not clinically meaningful) better QoL outcomes than those who had 1 or >1 treatment. CP-CML patients had better QoL than those with AP-CML and BC-CML. The scores on each subscale are predominantly consistent with a disease that has few symptoms at initial diagnosis and more as the number of treatments or phase of disease increases. |
| Whiteley et al26 | FACT-Leu; EQ-5D | To examine the effect of bosutinib on QoL in patients with advanced-phase CML (AP and BC) after imatinib failure. | In both the AP-CML and BC-CML cohorts, QoL impairments at baseline were minimal and statistically significant improvements in QoL were observed over the course of bosutinib treatment at multiple time points. Health status remained stable during treatment in AP-CML patients and statistically significant improvements were observed in BC-CML patients with bosutinib treatment; significant improvements were seen in VAS scores at several time points during treatment in both cohorts. This study did not have a control or comparison group, which limits the ability to attribute improvements in QoL specifically to bosutinib treatment. |
| PROs in CML patients switching or discontinuing therapy | |||
| Cortes et al27 | MDASI-CML, ad hoc 11-point scale for QoL assessment | To evaluate whether imatinib-related nonhematologic chronic low-grade AEs (grade 1 or 2) could be improved and responses optimized by switching patients from imatinib to nilotinib. | Switching from imatinib to nilotinib led to improvements in imatinib-related AEs in most patients. Within 1 mo after switching to nilotinib, most imatinib-related AEs had either resolved or improved, and by 3 mo, the frequency of the AEs that had improved increased further. New AEs were reported during nilotinib therapy, including SAEs; however, the overall QoL and MDASI-CML scores generally improved throughout the study. Nilotinib therapy also resulted in effective disease control, as evidenced by the maintenance and/or achievement of CyR and MR in most patients. |
| Park et al28 | Ad hoc questionnaire composed of 43 parameters (22 imatinib-related AEs, 11 physical and 10 mental health-related parameters modified from FACT-Leu and SF-36) | To investigate the changes in health-related profiles including QoL occurring in CP-CML patients who discontinued imatinib after achieving sustained undetectable molecular residual disease (observation time, 6 mo). | Most symptoms and signs (such as nausea, indigestion, peripheral edema, skin whitening, and fragility) rapidly resolved in a higher proportion of patients. However, interestingly, key symptoms, such as musculoskeletal pain, pruritus, and fatigue were newly developed or worsened in some patients after imatinib discontinuation. Improvements in physical and mental health were variable in individual patients and were not significantly improved. |
| Reference . | PRO instruments . | Main objective . | Summary of conclusions and clinical implications . |
|---|---|---|---|
| PROs in CP-CML patients treated with first-line imatinib | |||
| Hahn et al21 | FACT-BRM; EQ-5D | To compare the impact of QoL in CP-CML patients receiving imatinib or IFN-α plus low-dose cytarabine (IRIS study). Crossover to the other treatment arm is permitted due to a lack of efficacy or treatment intolerance. | QoL outcomes are better with imatinib than IFN-α plus low-dose cytarabine as first-line therapy of CP-CML. A significant improvement in QoL also occurs in patients who cross over from IFN-α plus low-dose cytarabine to imatinib. Physical function and well-being and social and family well-being are better among men than among women. |
| Efficace et al22 | SF-36 plus ad hoc 9-item symptom checklist | To investigate whether CP-CML patients in treatment with long-term therapy (at least 3 y) with first-line imatinib have a different QoL profile compared with the general population. | Patients aged ≥60 y have a QoL profile very similar to that reported by their respective peers (without cancer) in the general population. However, younger patients aged 18–59 y report clinically meaningful impairments in most aspects of QoL, in particular in role limitations because of physical and emotional problems. Women have a worse profile than men when each patient was compared with his or her peer in the general population. Fatigue is the most prevalent symptom. |
| Efficace et al23 | SF-36; FACIT-Fatigue; MSPSS | To investigate factors associated with long-term QoL outcomes of CP-CML patients in CCyR treated with imatinib therapy, and to investigate the relationships between fatigue and other treatment-related symptoms. | Fatigue is the main factor independently associated with long-term QoL of CML patients. Even small variation in fatigue severity corresponded to clinically meaningful impairments in overall QoL. Fatigue in this population does not occur by itself but clusters with other symptoms (mainly musculoskeletal pain and muscular cramps). |
| PROs in CML patients also treated with second-generation TKIs or in advanced phase (AP or BC) | |||
| Trask et al25 | FACT-Leu | To assess the impact of bosutinib treatment (until disease progression, unmanageable toxicity, or withdrawal of consent at the various time points) on the QoL of imatinib-resistant and imatinib-intolerant CP-CML patients. | CP-CML patients have little impairment in most aspects of QoL at the start of treatment. At baseline, there were no apparent differences in the FACT-Leu scales between imatinib-resistant and imatinib-intolerant CP-CML patients. Over the course of bosutinib therapy, only imatinib-intolerant CP-CML patients showed statistically significant and clinically meaningful improvements on several FACT-Leu scales. |
| Trask et al24 | FACT-Leu | To provide information on the QoL of CP-CML patients prior to first-line, second-line, and third-line therapy, and to provide the same information for those patients previously treated in the AP and BC of the disease. | CP-CML patients about to receive first-line treatment reported statistically significant (but not clinically meaningful) better QoL outcomes than those who had 1 or >1 treatment. CP-CML patients had better QoL than those with AP-CML and BC-CML. The scores on each subscale are predominantly consistent with a disease that has few symptoms at initial diagnosis and more as the number of treatments or phase of disease increases. |
| Whiteley et al26 | FACT-Leu; EQ-5D | To examine the effect of bosutinib on QoL in patients with advanced-phase CML (AP and BC) after imatinib failure. | In both the AP-CML and BC-CML cohorts, QoL impairments at baseline were minimal and statistically significant improvements in QoL were observed over the course of bosutinib treatment at multiple time points. Health status remained stable during treatment in AP-CML patients and statistically significant improvements were observed in BC-CML patients with bosutinib treatment; significant improvements were seen in VAS scores at several time points during treatment in both cohorts. This study did not have a control or comparison group, which limits the ability to attribute improvements in QoL specifically to bosutinib treatment. |
| PROs in CML patients switching or discontinuing therapy | |||
| Cortes et al27 | MDASI-CML, ad hoc 11-point scale for QoL assessment | To evaluate whether imatinib-related nonhematologic chronic low-grade AEs (grade 1 or 2) could be improved and responses optimized by switching patients from imatinib to nilotinib. | Switching from imatinib to nilotinib led to improvements in imatinib-related AEs in most patients. Within 1 mo after switching to nilotinib, most imatinib-related AEs had either resolved or improved, and by 3 mo, the frequency of the AEs that had improved increased further. New AEs were reported during nilotinib therapy, including SAEs; however, the overall QoL and MDASI-CML scores generally improved throughout the study. Nilotinib therapy also resulted in effective disease control, as evidenced by the maintenance and/or achievement of CyR and MR in most patients. |
| Park et al28 | Ad hoc questionnaire composed of 43 parameters (22 imatinib-related AEs, 11 physical and 10 mental health-related parameters modified from FACT-Leu and SF-36) | To investigate the changes in health-related profiles including QoL occurring in CP-CML patients who discontinued imatinib after achieving sustained undetectable molecular residual disease (observation time, 6 mo). | Most symptoms and signs (such as nausea, indigestion, peripheral edema, skin whitening, and fragility) rapidly resolved in a higher proportion of patients. However, interestingly, key symptoms, such as musculoskeletal pain, pruritus, and fatigue were newly developed or worsened in some patients after imatinib discontinuation. Improvements in physical and mental health were variable in individual patients and were not significantly improved. |
CyR, cytogenetic response; EQ-5D, Euro QoL (utility questionnaire reflecting the patient’s value of her or his current health state); FACIT-Fatigue: Functional Assessment of Chronic Illness Therapy fatigue scale; FACT-BRM, Functional Assessment of Cancer Therapy – Biologic Response Modifiers; FACT-Leu, Functional Assessment of Cancer Therapy – Leukemia; GI, gastrointestinal; IFN-α, interferon-α; MDASI-CML, MD Anderson Symptom Inventory Chronic Myeloid Leukemia Module; MR, molecular response; MSPSS, Multidimensional Scale of Perceived Social Support; SAE, serious adverse event; SF-36, 36-Item Short Form Health Survey; VAS, Visual Analog Scale Health State Today.