{"corpus_id":8302472,"paper_sha":"51e5e2cce6682c01b59bd7fa25ec76c89ce866a1","doi":"10.1200/JCO.2009.26.3087","arxiv_id":null,"pmid":20385986,"pmcid":"PMC6366340","mag_id":2166270808,"dblp_id":null,"acl_id":null,"title":"Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib.","year":2010,"publication_date":"2010-05-10","venue":"Journal of Clinical Oncology","journal":{"name":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","pages":"\n          2381-8\n        ","volume":"28 14"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine"],"reference_count":36,"citation_count":909,"influential_citation_count":60,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"ATP Binding Cassette Transporter, Subfamily B","mj":false,"ui":"D018435"},{"d":"ATP Binding Cassette Transporter, Subfamily B, Member 1","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D020168"},{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Aged, 80 and over","mj":false,"ui":"D000369"},{"d":"Antineoplastic Agents","mj":false,"qs":[{"q":"pharmacokinetics","mj":false,"ui":"Q000493"},{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D000970"},{"d":"Benzamides","mj":false,"ui":"D001549"},{"d":"Cytogenetic Analysis","mj":true,"ui":"D020732"},{"d":"Drug Monitoring","mj":false,"qs":[{"q":"instrumentation","mj":false,"ui":"Q000295"}],"ui":"D016903"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Fusion Proteins, bcr-abl","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D016044"},{"d":"Gene Expression Regulation, Leukemic","mj":true,"ui":"D015973"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Imatinib Mesylate","mj":false,"ui":"D000068877"},{"d":"Kaplan-Meier Estimate","mj":false,"ui":"D053208"},{"d":"Leukemia, Myelogenous, Chronic, BCR-ABL Positive","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D015464"},{"d":"Logistic Models","mj":false,"ui":"D016015"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Medication Adherence","mj":true,"ui":"D055118"},{"d":"Micro-Electrical-Mechanical Systems","mj":false,"qs":[{"q":"instrumentation","mj":false,"ui":"Q000295"}],"ui":"D055617"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Mutation","mj":false,"ui":"D009154"},{"d":"Octamer Transcription Factor-1","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D050811"},{"d":"Piperazines","mj":false,"qs":[{"q":"pharmacokinetics","mj":false,"ui":"Q000493"},{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D010879"},{"d":"Polymorphism, Genetic","mj":false,"ui":"D011110"},{"d":"Proportional Hazards Models","mj":false,"ui":"D016016"},{"d":"Protein Kinase Inhibitors","mj":false,"qs":[{"q":"pharmacokinetics","mj":false,"ui":"Q000493"},{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D047428"},{"d":"Pyrimidines","mj":false,"qs":[{"q":"pharmacokinetics","mj":false,"ui":"Q000493"},{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D011743"},{"d":"RNA, Messenger","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D012333"},{"d":"Risk Assessment","mj":false,"ui":"D018570"},{"d":"Risk Factors","mj":false,"ui":"D012307"},{"d":"Time Factors","mj":false,"ui":"D013997"},{"d":"Treatment Outcome","mj":false,"ui":"D016896"},{"d":"Young Adult","mj":false,"ui":"D055815"}],"chemicals":[{"n":"ABCB1 protein, human","ui":"C513055","reg":"0"},{"n":"ATP Binding Cassette Transporter, Subfamily B","ui":"D018435","reg":"0"},{"n":"ATP Binding Cassette Transporter, Subfamily B, Member 1","ui":"D020168","reg":"0"},{"n":"Antineoplastic Agents","ui":"D000970","reg":"0"},{"n":"Benzamides","ui":"D001549","reg":"0"},{"n":"Octamer Transcription Factor-1","ui":"D050811","reg":"0"},{"n":"POU2F1 protein, human","ui":"C494165","reg":"0"},{"n":"Piperazines","ui":"D010879","reg":"0"},{"n":"Protein Kinase Inhibitors","ui":"D047428","reg":"0"},{"n":"Pyrimidines","ui":"D011743","reg":"0"},{"n":"RNA, Messenger","ui":"D012333","reg":"0"},{"n":"abl-bcr fusion protein, human","ui":"C406060","reg":"0"},{"n":"Imatinib Mesylate","ui":"D000068877","reg":"8A1O1M485B"},{"n":"Fusion Proteins, bcr-abl","ui":"D016044","reg":"EC 2.7.10.2"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2009.26.3087","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/51e5e2cce6682c01b59bd7fa25ec76c89ce866a1","s2_open_access_license":null,"s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"PURPOSE: There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence. METHODS: Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.7 months (range, 25 to 104 months) who had achieved complete cytogenetic response had adherence monitored during a 3-month period by using a microelectronic monitoring device. Adherence was correlated with levels of molecular response. Other factors that could influence outcome were also analyzed. RESULTS: Median adherence rate was 98% (range, 24% to 104%). Twenty-three patients (26.4%) had adherence <or= 90%; in 12 of these patients (14%), adherence was <or= 80%. There was a strong correlation between adherence rate (<or= 90% or > 90%) and the 6-year probability of a 3-log reduction (also known as major molecular response [MMR]) in BCR-ABL1 transcripts (28.4% v 94.5%; P < .001) and also complete molecular response (CMR; 0% v 43.8%; P = .002). Multivariate analysis identified adherence (relative risk [RR], 11.7; P = .001) and expression of the molecular human organic cation transporter-1 (RR, 1.79; P = .038) as the only independent predictors for MMR. Adherence was the only independent predictor for CMR. No molecular responses were observed when adherence was <or= 80% (P < .001). Patients whose imatinib doses were increased had poor adherence (86.4%). In this latter population, adherence was the only independent predictor for inability to achieve an MMR (RR, 17.66; P = .006). CONCLUSION: In patients with CML treated with imatinib for some years, poor adherence may be the predominant reason for inability to obtain adequate molecular responses.","claims":[{"public_id":"cl_29d81a541e2b3fd943943d662bc7fdd3","status":"active","text":"Adherence is strongly associated with major molecular response and complete molecular response in chronic-phase chronic myeloid leukemia patients treated with imatinib after complete cytogenetic response.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_29d81a541e2b3fd943943d662bc7fdd3"},{"public_id":"cl_773d9cb3ad55e341efdaf2cef22556dc","status":"active","text":"Adherence is the only independent predictor of complete molecular response, and together with molecular human organic cation transporter-1 expression it predicts major molecular response.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_773d9cb3ad55e341efdaf2cef22556dc"},{"public_id":"cl_513718abcf066ce3ce611ea269ab72a2","status":"active","text":"Adherence of 90% or less is associated with substantially lower 6-year probabilities of major molecular response and complete molecular response than adherence above 90%.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_513718abcf066ce3ce611ea269ab72a2"},{"public_id":"cl_c5bd1500da386f8bdbdc5d371d0a0d49","status":"active","text":"No molecular responses were observed when adherence was 80% or less.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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thresholds analyzed.","types":["measure"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_92bd9acc4103889517cfc2297306f2eb"},{"public_id":"co_97acd5995d5308e3cad2847a0c1695dc","status":"active","name":"molecular response","description":"The reduction or disappearance of BCR-ABL1 transcript levels used to evaluate treatment effect.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_97acd5995d5308e3cad2847a0c1695dc"},{"public_id":"co_9b4b99f3d419364352377bc9d2ae34d8","status":"active","name":"microelectronic monitoring device","description":"An electronic device used to record medication-taking behavior over the 3-month monitoring 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