Meeting NewsPerspective

Smoking associated with poorer-risk cytogenetics, worse survival in acute myeloid leukemia

CHICAGO — Smoking appeared associated with poorer-risk molecular profiles and cytogenetics, lower response rates and worse OS among treatment-naive patients with acute myeloid leukemia, according to results of a single-center retrospective study presented at ASCO Annual Meeting.

“From prior studies we know that smoking is a risk factor for the development of AML and we know that it is genetically impacting patients,” Mansour Alfayez, MD, fellow at The University of Texas MD Anderson Cancer Center, said during a presentation. “However, the details on how and why are not completely clear.”

Smoking increases the risk for AML by 40% among active smokers and 25% among former smokers compared with nonsmokers.

Alfayez and colleagues analyzed the correlation between smoking and underlying AML biology and the impact of smoking on relapse risk and treatment outcomes among 561 newly diagnosed patients with AML seen at The University of Texas MD Anderson Cancer Center between 2012 and 2017. The researchers evaluated smoking history, co-occurring mutations, cytogenetics and clinical outcomes. They grouped patients according to smoking status, with 272 former and active (ever) smokers (median age, 69 years; range, 22-92; 53% men) and 289 never smokers (median age, 63 years; range, 18-97; 45% men).

Alfayez and colleagues found smoking was significantly associated with several risk factors, including:

  • age older than 60 years (OR = 2.57; 95% CI, 1.8-3.68);
  • complex karyotype (OR = 2.14; 95% CI, 1.44-3.22);
  • male sex (OR = 1.95; 95% CI, 1.39-2.73);
  • ASXL1 mutation (OR = 1.94; 95% CI, 1.15-3.34);
  • TP53 mutation (OR = 1.68; 95% CI, 1.07-2.65);
  • favorable European LeukemiaNet (ELN) criteria vs. intermediate vs. adverse risk (OR = 1.57; 95% CI, 0.96-2.58);
  • secondary AML (OR = 1.56; 95% CI, 1.05-2.33); and
  • dysplasia (OR = 1.5; 95% CI, 1.06-2.11).
  • The researchers observed negative associations between smoking and:
  • NPM1 mutation(OR = 0.65; 95% CI, 0.42-0.98);
  • FLT3-ITD negativity (OR = 0.75; 95% CI, 0.57-0.97);
  • high vs. low treatment intensity (OR = 0.53; 95% CI, 0.38-0.74);
  • core binding factor (OR = 0.28; 95% CI, 0.1-0.67);
  • CBFB-MYH11 positivity (OR = 0.28; 95% CI, 0.06-0.93); and
  • GATA2 positivity (OR = 0.27; 95% CI, 0.06-0.88).

In an analysis controlled for age, the associations remained significant between smoking and ELN risk (P = .041), complex karyotype (P < .0001), dysplasia (P = .037) and GATA2 (P = .045), but not for FLT3-ITD, NPM1 and TP53.

Univariate regression analyses showed significant associations between smoking and shorter OS (P < .0001) among treatment-naive patients.

Smoking also was associated with lower odds of achieving clinical response to treatment (OR = 0.6; 95% CI, 0.41-0.88). Cumulative incidence of relapse occurred among 43% of ever-smokers compared with 30% of never-smokers (P = .0091).

However, after controlling for age and performance status, multivariate Cox regression for survival showed smoking yielded an HR of 1.42 (95% CI, 1.08-1.86), but response showed an HR of 0.62 (95% CI, 0.4-1.04).

Researchers observed no association between smoking and number of mutations.

Researchers’ inability to quantify smoking exposure and assess the impact of smoking cessation and duration served as the study’s limitations. Other limitations included the study’s retrospective nature and a limited genomic panel.

“Smoking is associated with older age, adverse risk cytogenetics and molecular profile,” Alfayez said during the presentation. “AML in smokers is associated with worse survival and higher incidence of relapse, independent of age and performance status.” – by John DeRosier

Reference:

Alfayez M, et al. Abstract 7002. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Alfayez reports no relevant financial disclosures. Please see the abstract for all relevant financial disclosures.

CHICAGO — Smoking appeared associated with poorer-risk molecular profiles and cytogenetics, lower response rates and worse OS among treatment-naive patients with acute myeloid leukemia, according to results of a single-center retrospective study presented at ASCO Annual Meeting.

“From prior studies we know that smoking is a risk factor for the development of AML and we know that it is genetically impacting patients,” Mansour Alfayez, MD, fellow at The University of Texas MD Anderson Cancer Center, said during a presentation. “However, the details on how and why are not completely clear.”

Smoking increases the risk for AML by 40% among active smokers and 25% among former smokers compared with nonsmokers.

Alfayez and colleagues analyzed the correlation between smoking and underlying AML biology and the impact of smoking on relapse risk and treatment outcomes among 561 newly diagnosed patients with AML seen at The University of Texas MD Anderson Cancer Center between 2012 and 2017. The researchers evaluated smoking history, co-occurring mutations, cytogenetics and clinical outcomes. They grouped patients according to smoking status, with 272 former and active (ever) smokers (median age, 69 years; range, 22-92; 53% men) and 289 never smokers (median age, 63 years; range, 18-97; 45% men).

Alfayez and colleagues found smoking was significantly associated with several risk factors, including:

  • age older than 60 years (OR = 2.57; 95% CI, 1.8-3.68);
  • complex karyotype (OR = 2.14; 95% CI, 1.44-3.22);
  • male sex (OR = 1.95; 95% CI, 1.39-2.73);
  • ASXL1 mutation (OR = 1.94; 95% CI, 1.15-3.34);
  • TP53 mutation (OR = 1.68; 95% CI, 1.07-2.65);
  • favorable European LeukemiaNet (ELN) criteria vs. intermediate vs. adverse risk (OR = 1.57; 95% CI, 0.96-2.58);
  • secondary AML (OR = 1.56; 95% CI, 1.05-2.33); and
  • dysplasia (OR = 1.5; 95% CI, 1.06-2.11).
  • The researchers observed negative associations between smoking and:
  • NPM1 mutation(OR = 0.65; 95% CI, 0.42-0.98);
  • FLT3-ITD negativity (OR = 0.75; 95% CI, 0.57-0.97);
  • high vs. low treatment intensity (OR = 0.53; 95% CI, 0.38-0.74);
  • core binding factor (OR = 0.28; 95% CI, 0.1-0.67);
  • CBFB-MYH11 positivity (OR = 0.28; 95% CI, 0.06-0.93); and
  • GATA2 positivity (OR = 0.27; 95% CI, 0.06-0.88).

In an analysis controlled for age, the associations remained significant between smoking and ELN risk (P = .041), complex karyotype (P < .0001), dysplasia (P = .037) and GATA2 (P = .045), but not for FLT3-ITD, NPM1 and TP53.

Univariate regression analyses showed significant associations between smoking and shorter OS (P < .0001) among treatment-naive patients.

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Smoking also was associated with lower odds of achieving clinical response to treatment (OR = 0.6; 95% CI, 0.41-0.88). Cumulative incidence of relapse occurred among 43% of ever-smokers compared with 30% of never-smokers (P = .0091).

However, after controlling for age and performance status, multivariate Cox regression for survival showed smoking yielded an HR of 1.42 (95% CI, 1.08-1.86), but response showed an HR of 0.62 (95% CI, 0.4-1.04).

Researchers observed no association between smoking and number of mutations.

Researchers’ inability to quantify smoking exposure and assess the impact of smoking cessation and duration served as the study’s limitations. Other limitations included the study’s retrospective nature and a limited genomic panel.

“Smoking is associated with older age, adverse risk cytogenetics and molecular profile,” Alfayez said during the presentation. “AML in smokers is associated with worse survival and higher incidence of relapse, independent of age and performance status.” – by John DeRosier

Reference:

Alfayez M, et al. Abstract 7002. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Alfayez reports no relevant financial disclosures. Please see the abstract for all relevant financial disclosures.

    Perspective
    Jamie L. Koprivnikar

    Jamie L. Koprivnikar

    The results of this study weren’t particularly surprising. We know from a large meta-analysis published in 2014 that cigarette smoking is associated with an increased risk for AML, and this study showed that patients who are current or former smokers have inferior outcomes compared with their nonsmoking peers in the upfront setting.

    An interesting thing about this study is that it elicits the mechanism of this difference in treatment outcomes. There are two reasons why smokers have worse outcomes: one is that they have compromised lung and other organ function, the other is that smoking may promote a more severe disease biology. The results of this study indicate that patients who are smokers have higher-risk forms of leukemia.

    Nonsmokers who develop lung cancer are more likely to have a less-aggressive form of cancer and a higher likelihood of responding to targeted therapies. So, I think we will see similar results across other cancer types. We don’t have as clearly defined statistics in other cancers, but if we look closely, I think we will see that it applies in a lot of situations.

    • Jamie L. Koprivnikar, MD
    • Hackensack Meridian Health

    Disclosures: Koprivnikar reports no relevant financial disclosures.

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