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Patient-Reported Functional Outcomes in Patients With Chronic Myeloid Leukemia After Stopping Tyrosine Kinase Inhibitors.

ABSTRACT: Treatment-free remission (TFR) is a goal for patients with chronic myeloid leukemia (CML). Functional outcomes after discontinuing tyrosine kinase inhibitor (TKI) treatment have not been described. Patient-Reported Outcomes Measurement Information System (PROMIS) measures of social, physical, cognitive, and sexual function were assessed over 36 months in 172 adult patients with chronic phase CML from 14 sites at baseline (on TKI) and after discontinuation. Linear mixed-effects models described the average trajectories for each patient-reported outcome measure after discontinuation and in those who restarted TKI. Of 112 patients in TFR at 12 months, 103 (92.0%) had a 3-point or greater improvement in social function, 80 (71.4%) in social isolation, 11 (9.8%) in satisfaction with sex life, 4 (3.6%) in physical function, and no patients had a 3-point or greater improvement in cognitive function or interest in sexual activity. Patients' scores worsened after restarting TKI. This novel information on functional outcomes in TFR can help guide patient and clinician decision making.

SUBMITTER: Schoenbeck KL

PROVIDER: S-EPMC8755495 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Patient-Reported Functional Outcomes in Patients With Chronic Myeloid Leukemia After Stopping Tyrosine Kinase Inhibitors.

Schoenbeck Kelly L KL Atallah Ehab E Lin Li L Weinfurt Kevin P KP Cortes Jorge J Deininger Michael W N MWN Kota Vamsi V Larson Richard A RA Mauro Michael J MJ Oehler Vivian G VG Pinilla-Ibarz Javier J Radich Jerald P JP Schiffer Charles A CA Shah Neil P NP Silver Richard T RT Thompson James E JE Flynn Kathryn E KE

Journal of the National Cancer Institute 20220101 1

Treatment-free remission (TFR) is a goal for patients with chronic myeloid leukemia (CML). Functional outcomes after discontinuing tyrosine kinase inhibitor (TKI) treatment have not been described. Patient-Reported Outcomes Measurement Information System (PROMIS) measures of social, physical, cognitive, and sexual function were assessed over 36 months in 172 adult patients with chronic phase CML from 14 sites at baseline (on TKI) and after discontinuation. Linear mixed-effects models described t ...[more]

PMID: 34491344

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Project description:ImportanceTyrosine kinase inhibitors (TKIs) have been associated with improved survival of patients with chronic myeloid leukemia (CML) but are also associated with adverse effects, especially fatigue and diarrhea. Discontinuation of TKIs is safe and is associated with the successful achievement of treatment-free remission (TFR) for some patients.ObjectiveTo evaluate molecular recurrence (MRec) and patient-reported outcomes (PROs) after TKI discontinuation for US patients with CML.Design, setting, and participantsThe Life After Stopping TKIs (LAST) study was a prospective single-group nonrandomized clinical trial that enrolled 172 patients from 14 US academic medical centers from December 18, 2014, to December 12, 2016, with a minimum follow-up of 3 years. Participants were adults with chronic-phase CML whose disease was well controlled with imatinib, dasatinib, nilotinib, or bosutinib. Statistical analysis was performed from August 13, 2019, to March 23, 2020.InterventionDiscontinuation of TKIs.Main outcomes and measuresMolecular recurrence, defined as loss of major molecular response (BCR-ABL1 International Scale ratio >0.1%) by central laboratory testing, and PROs (Patient-Reported Outcomes Measurement Information System computerized adaptive tests) were monitored. Droplet digital polymerase chain reaction (ddPCR) was performed on samples with undetectable BCR-ABL1 by standard real-time quantitative polymerase chain reaction (RQ-PCR).ResultsOf 172 patients, 89 were women (51.7%), and the median age was 60 years (range, 21-86 years). Of 171 patients evaluable for molecular analysis, 112 (65.5%) stayed in major molecular response, and 104 (60.8%) achieved TFR. Undetectable BCR-ABL1 by either ddPCR or RQ-PCR at the time of TKI discontinuation (hazard ratio, 3.60; 95% CI, 1.99-6.50; P < .001) and at 3 months (hazard ratio, 5.86; 95% CI, 3.07-11.1; P < .001) was independently associated with MRec. Molecular recurrence for patients with detectable BCR-ABL1 by RQ-PCR was 50.0% (14 of 28), undetectable BCR-ABL1 by RQ-PCR but detectable by ddPCR was 64.3% (36 of 56), and undetectable BCR-ABL1 by both ddPCR and RQ-PCR was 10.3% (9 of 87) (P ≤ .001). Of the 112 patients in TFR at 12 months, 90 (80.4%) had a clinically meaningful improvement in fatigue, 39 (34.8%) had a clinically meaningful improvement in depression, 98 (87.5%) had a clinically meaningful improvement in diarrhea, 24 (21.4%) had a clinically meaningful improvement in sleep disturbance, and 5 (4.5%) had a clinically meaningful improvement in pain interference. Restarting a TKI resulted in worsening of PROs.Conclusions and relevanceIn this study, TKI discontinuation was safe, and 60.8% of patients remained in TFR. Discontinuation of TKIs was associated with improvements in PROs. These findings should assist patients and physicians in their decision-making regarding discontinuation of TKIs. Detectable BCR-ABL1 by RQ-PCR or ddPCR at the time of TKI discontinuation was associated with higher risk of MRec; clinical application of this finding should be confirmed in other studies.Trial registrationClinicalTrials.gov Identifier: NCT02269267.

Project description:BackgroundThe objective of this study was to assess patient-reported outcomes (PROs), including health-related quality of life (HRQoL) and anxiety and depression symptoms, and to identify associated variables in patients with tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML) in chronic-phase (CP) or accelerated-phase (AP) who were receiving olverembatinib.MethodsPatients in multicenter studies were invited to complete the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 Questionnaire, the Self-Rating Anxiety Scale, and the Self-Rating Depression Scale at baseline and regularly during olverembatinib therapy. The time trends in PROs were estimated with a linear model using a generalized estimating equation based on an independent working correlation matrix. A generalized estimating equation model was used to assess the variables associated with PROs.ResultsIn total, 146 patients with CML-CP or CML-AP were included in this study. Scores on seven items from the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 Questionnaire, including global health, physical functioning, emotional functioning, fatigue, dyspnea, diarrhea, and financial difficulties, improved significantly over time during olverembatinib therapy. In multivariate analysis, age younger than 40 years was significantly associated with greater improvement in social functioning (p = .033), and CML-CP (vs. CML-AP) was associated with greater improvements in dyspnea (p = .031) and diarrhea (p = .031) over time. Scores on the Self-Rating Anxiety Scale and the Self-Rating Depression Scale decreased significantly over time during olverembatinib treatment (p < .001).ConclusionsThe authors concluded that HRQoL significantly improved over time during olverembatinib therapy in heavily treated patients with TKI-resistant CML, especially among those who were younger and those who had CML-CP. Anxiety symptoms also significantly decreased over time.

Project description:IntroductionChronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors.MethodsParallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced.ResultsAmong the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians' recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6-36]. Most (91.8%) physicians agreed that the breakpoint cluster region-Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians' recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients' adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients' mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group.ConclusionsOvercoming challenges in patient-physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income.Trial registrationClinicalTrials.gov identifier NCT05092048.

Dataset Information

Patient-Reported Functional Outcomes in Patients With Chronic Myeloid Leukemia After Stopping Tyrosine Kinase Inhibitors.

Publications

Patient-Reported Functional Outcomes in Patients With Chronic Myeloid Leukemia After Stopping Tyrosine Kinase Inhibitors.

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