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December 14, 2018
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Improvement in acute promyelocytic leukemia survival driven by reduction in early mortality

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Photo of Luciano Costa 2018
Luciano J. Costa

SAN DIEGO — Rates of early mortality have decreased, while OS has increased, among patients with acute promyelocytic leukemia in the United States, according to results of a population-based study presented at ASH Annual Meeting and Exposition.

However, these benefits have not extended to rural areas, or to older patients with acute promyelocytic leukemia (APL), results showed.

Prognosis for patients with APL has improved in clinical trials due to the use of all-trans retinoic acid and arsenic trioxide, with recent trials reporting over 90% long-term survival rates, according to study background.

“APL is distinct among acute leukemias due to the unique biology and very high cure rates,” Luciano J. Costa, MD, PhD, associate professor of medicine in the Blood and Marrow Transplantation and Cell Therapy Program at University of Alabama at Birmingham School of Medicine, said during his presentation. “However, APL patients often present with thrombotic or hemorrhagic complications, making early mortality a major component of treatment failure. Those patients, therefore, usually require very expert diagnosis, as well as peculiar and complex management.

“It is not well known if disease awareness, access to specialized care, improvement in supportive care and availability of less-toxic treatments have impacted risk for early mortality in the last 2 decades,” Costa added.

Costa and colleagues used 1992 to 2015 SEER data to determine trends in early mortality — defined as death in the first 30 days, irrespective of cause — over the past 2 decades in the U.S. among 2,224 patients (median age, 45 years; 49% male; 55.2% white) with APL.

Researchers divided patients into those aged younger than 40 years (n = 895) and those aged 40 years or older (n = 1,329). They calculated OS and early mortality for consecutive 4-year eras.

Median follow-up was 41 months (range, 0-287).

Overall, researchers noted a reduction in the rate of early mortality, from 31.5% in 1992 to 1995 to 15.9% in 2012 to 2015 (P < .001).

The early mortality rate declined from 27.4% to 5.4% (P < .001) among the younger age group, and from 35.2% to 22.2% (P = .02) among the older age group during those periods.

“This trend was very heterogenous, being very pronounced among children, adolescents and young adults, reaching a level of 5.4% in the most recent cohort,” Costa said. “Among older adults, however, although there has been a decline, it has not been as pronounced, and we are still dealing with an unacceptable high rate of mortality.”

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Subgroup analyses showed race and ethnicity did not appear to influence the trend for reduction, nor did gender and county-level educational achievement, Costa said.

Early mortality rates declined significantly among residents of urban areas (30.2% vs. 14.8%; P = .001), but not among residents of rural areas (38.7% vs. 22.1%).

“Although we saw a nonsignificant reduction among residents of rural counties, this may in part be due to the relatively low number of patients; only 14% of patients were in this group, with very wide confidence intervals,” Costa said.

When researchers evaluated OS, they observed a major improvement in the mid-to-late 1990s, likely related to the introduction of new therapies, with incremental gains thereafter, Costa said.

Overall, 3-year OS rates improved from 49.2% to 76.4%, with higher rates of early mortality driving the poorer OS in earlier eras.

Researchers also conducted landmark OS analyses, for which they looked at patients who achieved 1-month OS after diagnosis. This analysis also showed an improvement in OS over time (3-year OS, 71.9% vs. 90.8%), but not to the same magnitude as analyses that did not adjust for early mortality.

“This analysis also gives us the perspective of what the outcomes would be if we could completely overcome early mortality,” Costa said. “The data show us how many patients are dying just because we cannot successfully diagnosis and manage them during the first month.” – by Alexandra Todak

Reference:

Xavier AC, et al. Abstract 710. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4; 2018; San Diego.

Disclosures: Costa reports honoraria or research funding from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Karyopharm and Sanofi. The other authors report no relevant financial disclosures.