Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial.

In ASCEMBL, an open-label, randomized Phase 3 study, asciminib demonstrated superior efficacy and better safety profile compared with bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors. Health-related quality of life (HRQOL) reported by patients is key to understanding the benefit and impact of treatment on patients' lives, and is becoming increasingly important as the life expectancy of CML-CP patients increases and patients require long-term treatment. In ASCEMBL, patients completed questionnaires to assess CML symptoms and interference with daily life (M.D. Anderson Symptom Inventory - CML [MDASI-CML]), general HRQOL (five-level EQ-5D [EQ-5D-5L], Patient Global Impression of Change - CML [PGIC-CML]), and impact of CML on working life and activity (Work Productivity and Activity Impairment questionnaire - CML [WPAI-CML]). Patients' CML symptoms and HRQOL remained stable during 48 weeks of treatment with asciminib, with a general trend for decreased CML symptom severity, particularly for fatigue, and improvement in HRQOL. A clinically meaningful increase in diarrhea severity was observed in patients treated with bosutinib compared to asciminib. These data provide better understanding of the patient perspective and treatment impact on HRQOL in a later-line setting, where little information has been published to date.

The impact of COVID-19 on patients with hematological malignancies: the mixed-method analysis of an Israeli national survey.

BACKGROUND: The COVID-19 pandemic required reevaluation of the therapeutic approach and added emotional stress for patients with hematological malignancies at high risk of contracting the virus. We aimed to evaluate how it affected such patients during the second lockdown in Israel. METHODS: This national survey included Hebrew-speaking patients with hematological malignancy. This included three tools with 28 items of sociodemographic and medical baseline characteristics, management of hematological disease, and evaluation of emotional coping during COVID-19 pandemic; the Hebrew version of the Patient Health Questionnaire 9; and 3 qualitative open-ended questions. Data was analyzed by mixed methods which combined both quantitative and qualitative thematic analyses. RESULTS: Four hundred eight patients responded to the survey. The management of their hematological disease included a decrease in the number of visits to the hematology clinic (37.0%), delay of some treatment schedules (9.1%), and prescription of replacement therapies permitting less visits to the clinic (2.2%). The frequency and intensity of "feeling afraid" regarding COVID-19 infection was increased (mean ± SD: 4 ± 1 to 5 ± 2 in a 1-7 Likert scale), and a high rate of depression was recorded, which appeared to be more evident in patients with chronic myeloid leukemia (CML) (p < 0.001). CONCLUSION: The management of hematological malignancies during pandemics should always take into consideration patients' fears, as well as the development of depression related to isolation and loneliness, in addition to the high risk of severe disease. Patients with CML had a high rate of depression which obviously needs to be managed very carefully during and after the COVID-19 pandemic.

Health-Related Quality of Life in Patients with Chronic Myeloid Leukemia Treated with First- Versus Second-Generation Tyrosine Kinase Inhibitors.

The life expectancy of patients with chronic myeloid leukemia (CML) approaches that of the age-matched population and quality of life (QOL) issues are becoming increasingly important. To describe patients' characteristics and assess QOL, we delivered a 30-item core questionnaire, a 24-item CML-specific questionnaire, both from the European Organization for Research and Treatment of Cancer (EORTC), and additional health-related items to 350 patients. Among 193 patients who completed the questionnaires, 139 received either imatinib (n = 70, 33%), dasatinib (n = 45, 23%) or nilotinib (n = 24, 12%). Patients' median age was 58 (range: 23 to 89) years and 86 (63%) were males. Stratifying patients by treatment, we recognized two distinct populations. In comparison to patients on dasatinib and nilotinib, patients on imatinib were two decades older, had a longer duration of disease and current treatment, experienced fewer limitations on daily activities (p = 0.02), less fatigue (p = 0.001), lower degree of impaired body image (p = 0.022) and less painful episodes (p = 0.014). Similarly, they had better emotional functioning, were less worried, stressed, depressed or nervous (p = 0.01) and were more satisfied with their treatment (p = 0.018). Not only does age associate with current treatments, but it also predicts how patients perceive QOL. Young patients express impaired QOL compared with elderly patients.

Treatment-free remission in chronic myeloid leukemia: the patient perspective and areas of unmet needs.

In CML, treatment-free remission (TFR) refers to having a stable deep molecular response without the need for ongoing tyrosine kinase inhibitor treatment. Whilst recommendations exist about the technical management of stopping and re-starting therapy, much is still unknown about the experiences of those considering and undertaking TFR. This study sought to obtain the patient perspective, identify areas of unmet needs and create recommendations for improvements. Fifty-six percent of patients reported fear or anxiety during treatment discontinuation, whereas only 7% of patients were asked if they needed psychological support during this period. Where patients re-initiated treatment; 59% felt scared or anxious, and 56% felt depressed. Twenty-six percent of re-initiated patients received psychological and/or emotional support at this time. Sixty percent of patients experienced withdrawal symptoms whilst discontinuing treatment, however, 40% of patients who experienced withdrawal symptoms reported that they were not fully supported by their doctor in managing all the symptoms. Healthcare professionals should further consider how they monitor the psychological well-being of patients who are discontinuing or re-initiating treatment, and review what support is offered in response to identified concerns. Surveillance of withdrawal symptoms should be a priority during treatment discontinuation, along with how healthcare professionals assist in the management of these.

Identifying Tyrosine Kinase Inhibitor Nonadherence in Chronic Myeloid Leukemia: Subanalysis of TAKE-IT Pilot Study.

BACKGROUND: There are inconsistencies in reports on correlates for nonadherence (NA) to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). The diagnostic accuracy of subjective adherence measures using electronic monitoring (EM) as the reference standard is yet to be determined. This study aimed to evaluate correlates of TKI NA using EM and test the diagnostic accuracy of subjective adherence measures. PATIENTS AND METHODS: CML patients receiving a TKI for any duration were enrolled at 4 hematology institutes, and adherence was measured for 4 months. EM adherence was the reference adherence measure, expressed as the percentage of days with the drug taken as prescribed. Subjective adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) self-report and clinician-reported visual analog scale (VAS) at 2 time points. Baseline theory-derived correlates of NA were identified using single and multiple regression analysis. The diagnostic accuracy of BAASIS and clinician-reported VAS was tested against an exploratory EM NA cutoff of < 95%. RESULTS: The median EM adherence (n = 55) was 97.5% (range, 48-100%), while the 25th percentile was 92.1%. Lack of membership in a CML patient support group, living alone, and third-line treatment were associated with EM NA on multiple regression analysis. The BAASIS self-report (n = 94) had a sensitivity of 67% and a specificity of 71% for diagnosing NA, while clinician-reported VAS (n = 89) had a sensitivity of 78% and specificity of 42%. CONCLUSION: A quarter of patients had potentially clinically meaningful NA. These NA correlates and the BAASIS provide a basis for identifying nonadherent patients who can be targeted by interventions.

Effect of Adherence-enhancing Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia (TAKE-IT): A Quasi-experimental Pre-Post Intervention Multicenter Pilot Study.

BACKGROUND: Nonadherence to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has been associated with inferior outcomes. Scarce evidence exists on the effectiveness of adherence-enhancing interventions. The present pilot study evaluated the feasibility and effectiveness of an intervention to improve TKI adherence in adult CML patients. PATIENTS AND METHODS: Using a quasi-experimental pre-post intervention design, we included a convenience sample of 58 CML patients (median age, 60.5 years; interquartile range, 19) receiving TKI treatment in 4 hematology institutes in Israel (median previous treatment duration, 34 months; interquartile range, 60). Of the 58 patients, 36 (62%) were receiving first-line treatment. TKI adherence was assessed using electronic monitoring for 7 months (4 months for the baseline assessment and for 3 months after the intervention) and defined as the percentage of days with dosing taken as prescribed. The multilevel intervention combined training of health care workers and multiple behavioral change techniques (eg, motivational interviewing, feedback on electronic monitoring printouts, behavioral change techniques tailored to reasons for nonadherence). The baseline and postintervention adherence were compared using generalized estimating equation models. RESULTS: The median baseline electronically monitored adherence (n = 55) was 97.5% (range, 48%-100%). The odds of taking the drug daily as prescribed were 58% greater after intervention (odds ratio, 1.58; 95% confidence interval [CI], 1.16-2.15). Adherence improved by only 1.5% overall (95% CI, 0.1%-2.8%) but by 8.5% (i.e. from 71.2% average adherence before intervention, to 79.6% after; P = .04) in a subgroup of 10 nonadherent patients (baseline adherence < 90%). CONCLUSION: TKI adherence improved with our pilot intervention, mainly in patients with suboptimal baseline adherence.

Considerations for Treatment-free Remission in Patients With Chronic Myeloid Leukemia: A Joint Patient-Physician Perspective.

Treatment-free remission (TFR) after discontinuation of tyrosine kinase inhibitor therapy is now an emerging treatment goal for patients with chronic myeloid leukemia, who have achieved a deep and stable response to treatment. Although guidance is now available, patients' questions regarding this progressive concept have yet to be addressed. The overall aim of this European Steering Group is a patient-centered approach that educates patients on their treatment options, including TFR, facilitates better patient-physician relationships, and meets patients' emotional and psychological needs. The present report outlines 5 key topic areas on discontinuing tyrosine kinase therapy and the implications of TFR for patient-physician consideration: what TFR is; when TFR is appropriate; which patients might and might not be eligible for TFR; and patients' considerations for discontinuing therapy, such as tyrosine kinase withdrawal syndrome, potential psychological implications, molecular recurrence, and repeat treatment. This Steering Group advocates that patients with chronic myeloid leukemia should have access to high-quality, frequent molecular monitoring and be treated in a specialist center with appropriate medical and psychological support. As patient concerns with attempting TFR become forefront in patient-physician discussions, a greater number of eligible patients might be willing to discontinue therapy.

Factors influencing adherence in CML and ways to improvement: Results of a patient-driven survey of 2546 patients in 63 countries.

Optimal adherence to CML therapy is of key importance to maximize treatment effectiveness. Two clinical studies (ADAGIO and Hammersmith) have proven a clear correlation between adherence and achieving optimal treatment response and have revealed that non-adherence is common in CML patients (Marin et al. in J Clin Oncol 28(24):2381-2388, 2010, Noens et al. in Haematologica 99(33):437-447, 2014). The aim of this study is to assess the extent of suboptimal adherence and to investigate motivations and behavioural patterns of adherence in a worldwide patient sample. Questionnaires were provided by the CML Advocates Network and were filled in by patients online and offline. Patient characteristics, treatment and motivations were collected. Adherence was assessed by the 8-item Morisky Medication Adherence scale. Logistic regression models were fitted to investigate the influence of different factors on adherence. Overall, 2 546 questionnaires from 63 countries and 79 CML patient organisations were evaluable. 32.7% of participants were highly adherent, 46.5% were in the medium and 20.7% in the low adherence group. Factors increasing the probability of being in the high adherence group are older age, male sex, management of side effects, only one tablet per day and feeling well informed about CML by the doctor. More than 2 years since diagnosis were significantly lowering the chance as was the use of reminding tools. Living arrangements, multiple medication and personal payment obligations increased the probability to be at least in the medium adherent group. This is the most comprehensive study conducted to date to gain knowledge about factors causing non-adherence in CML. Better information on the disease, medication and management of side effects, supported by haematologists, is key to improve adherence.

International development of an EORTC questionnaire for assessing health-related quality of life in chronic myeloid leukemia patients: the EORTC QLQ-CML24.

BACKGROUND: Health-related quality of life (HRQOL) is a key aspect for chronic myeloid leukemia (CML) patients. The aim of this study was to develop a disease-specific HRQOL questionnaire for patients with CML to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30. PATIENTS AND METHODS: The process followed a predefined and systematic stepwise iterative process as defined by the EORTC guidelines for questionnaire development. The process was divided into 3 phases: (1) generation of relevant HRQOL issues, (2) operationalization of the HRQOL issues into a set of items, and (3) pretesting the questionnaire for relevance and acceptability. Descriptive statistics and psychometric analyses were also performed. RESULTS: Overall, 655 CML patients were enrolled in 10 countries including the USA and countries in Europe and Asia. Interviews with health-care professionals experienced in CML (n = 59) were also conducted. Results from the interviews, clinical experiences, and statistical analyses were used to develop the EORTC QLQ-CML24. The final module consists of 24 items assessing the following aspects: symptom burden, impact on daily life and on worry/mood, body image problems, and satisfaction with care and with social life. Internal consistency, assessed with Cronbach's alpha coefficients, ranged from 0.73 to 0.83 for the proposed scales. CONCLUSION: The EORTC QLQ-CML24 is an internationally developed HRQOL questionnaire for CML patients, and its implementation in clinical research and practice can provide important information to facilitate clinical decision-making.