Cause of Death in Resistant and Advanced Chronic Myeloid Leukemia (CML) Patients Treated with Tyrosine Kinase Inhibitors (TKIs)

• Published in: Blood 2014-12, Vol.124 (21), p.5524-5524
• Main Authors: McGarry, Lisa J, Burudpakdee, Chakkarin, Gala, Smeet, Seetasith, Arpamas, Nanavaty, Merena, Huang, Hui
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.5524.5524

▪ Background: With recent advances in CML management, newly-diagnosed chronic phase (CP)-CML patients may expect near-normal life expectancy on TKI treatment. However, patients resistant to prior TKIs and those with advanced disease may face a much poorer prognosis and higher likelihood of CML-related death. Objective: To estimate the proportion of deaths in treatment-resistant and advanced-stage CML attributed to disease progression versus treatment-related adverse events (AEs) and unrelated (background) causes. Methods: We conducted a systematic literature review of PubMed, conference proceedings, and grey literature for relevant articles published between January 1999 and January 2014, reporting cause of death in CML patients treated with an approved TKI after failing 1 (2nd-line) or 2 (3rd-line) prior lines of therapy in CP, or those with advanced or blast-phase disease (AP/BP). We excluded studies that did not report results by disease phase or therapy line and those with poor data quality for investigator-reported cause of death, which was categorized as "CML-related” disease progression, "treatment-related” AE, "unrelated” AE, and "unspecified” AE. Results: We identified 60 studies that qualified for systematic assessment. Among these, 7 reporting 2nd-line (n=1,926 patients), 2 reporting 3rd-line (n=144), and 6 reporting AP/BP (n=634) results met all selection criteria. Overall, 5%, 10% and 21% of 2nd-line, 3rd-line and AP/BP patients, respectively, died during study follow-up. For 2nd-line patients, CML-related was the investigator-reported cause of 44% of deaths, compared with 2% dying of treatment-related causes and the remainder of unrelated (3%) or unspecified (51%) AEs (Figure 1). In 3rd line, 71% of patients died of CML, versus 7% treatment–related, 14% unrelated and 7% unspecified. Similarly, for AP/BP patients, death from disease comprised 54%, versus 5% treatment-related (10% unrelated; 31% unspecified). Although we lacked patient-level follow-up data, we estimated overall yearly death rates of 2%, 6% and 13% for 2nd-line, 3rd-line and AP/BP, respectively, versus US census estimates of