title: Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.
abstract: Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs.
authors.affiliation: Baylor University Medical Center, Dallas, TX, USA. Electronic address: Edward.Pearson@baylorhealth.edu.
authors.forename: Edward
authors.initials: E
authors.lastname: Pearson
authors.affiliation: ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA. Electronic address: Lisa.McGarry@ariad.com.
authors.forename: Lisa
authors.initials: L
authors.lastname: McGarry
authors.affiliation: MKTXS Market Access Solutions, LLC., Raritan, NJ, USA. Electronic address: sgala@mktxs.com.
authors.forename: Smeet
authors.initials: S
authors.lastname: Gala
authors.affiliation: ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA. Electronic address: Christopher.Nieset@ariad.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nieset
authors.affiliation: MKTXS Market Access Solutions, LLC., Raritan, NJ, USA. Electronic address: mnanavaty@mktxs.com.
authors.forename: Merena
authors.initials: M
authors.lastname: Nanavaty
authors.affiliation: MKTXS Market Access Solutions, LLC., Raritan, NJ, USA. Electronic address: mmwamburi@mktxs.com.
authors.forename: Mkaya
authors.initials: M
authors.lastname: Mwamburi
authors.affiliation: Baylor University Medical Center, Dallas, TX, USA. Electronic address: Moshe.Levy@BaylorHealth.edu.
authors.forename: Yair
authors.initials: Y
authors.lastname: Levy
mesh_terms: D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality* / Q000628:therapy*; D008297:Male; D015996:Survival Rate
keywords: Chronic myeloid leukemia; Chronic phase; Disease progression; Mortality; Treatment-related adverse events