Changing Molecular Diagnostic Testing Patterns for Patients (Pts) with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) in the Connect® MDS/AML Disease Registry

Introduction: Diagnosis of MDS and AML requires an integrated approach based on morphologic, cytogenetic, and molecular genetic tests to inform prognosis and treatment decisions. The World Health Organization (WHO) updated its classification criteria for MDS and AML in 2016 (Arber DA, et al. Blood. 2016;127:2391-2405). However, the impact of these criteria on diagnostic testing patterns in routine clinical practice is unknown. We investigated molecular testing patterns for pts with MDS and AML treated in academic (AC) or community/government (CO/GOV) sites in the Connect^® MDS/AML Registry.

Methods: The Connect^® MDS/AML Disease Registry (NCT01688011) is a large, ongoing, prospective, observational cohort study of pts with MDS aged ≥ 18 years or AML aged ≥ 55 years. Demographic and baseline characteristics and laboratory testing data were collected from pts enrolled in the Registry between December 12, 2013 and the data cutoff for this analysis of December 13, 2019. Patterns of molecular diagnostic testing were compared between the MDS and AML cohorts and between pts enrolled before January 1, 2017 and from January 1, 2017 onward. Logistic regression was used to identify factors associated with increased molecular diagnostic testing in the MDS and AML cohorts.

Results: As of December 13, 2019, 800 pts with MDS and 626 pts with AML were enrolled. Pts with MDS had a median age of 74 years (range 19–95); 49.0% were aged ≥ 75 years and 29.3% were aged ≥ 80 years. 66.3% of pts with MDS were male and 73.5% were insured by Medicare/Medicaid. Pts with AML had a median age of 71 years (range 55–97), 32.9% were aged ≥ 75 years and 14.9% were aged ≥ 80 years. 61.5% of pts with AML were male and 60.2% were insured by Medicare/Medicaid. Most pts in each cohort were treated at CO sites (MDS: 79.4%; AML: 57.0%). A smaller proportion of pts underwent molecular testing in the MDS cohort than in the AML cohort (29.1% vs 77.5%; P < 0.01). Molecular testing rates increased in both cohorts after January 1, 2017. Of 380 pts with MDS enrolled before January 1, 2017, 16.8% had molecular testing, increasing to 40.2% of 420 pts enrolled from January 1, 2017 onward (P < 0.01). Of 289 pts with AML enrolled before January 1, 2017, 68.9% had molecular testing, increasing to 84.9% of 337 pts enrolled from January 1, 2017 onward (P < 0.01). The number of mutations tested was higher in the MDS cohort than in the AML cohort (mean 11.1 vs 8.6; P < 0.01). The mean number of mutations tested increased from 6.9 before January 1, 2017 to 12.7 from January 1, 2017 onward in the MDS cohort (P < 0.01) and from 6.1 to 10.4, respectively, in the AML cohort (P < 0.01). Of the 11 mutations most frequently tested from January 1, 2017 onward in pts with MDS and AML, 0% and 36%, respectively, have US Food and Drug Administration-approved targeted therapies. The most common mutations tested were TP53 and ASXL1 in pts with MDS and FLT3-ITD and FLT3-TKD in pts with AML (Table). Testing rates for specific mutations increased when comparing pts enrolled before January 1, 2017 and pts enrolled from January 1, 2017 onwards: from 53.1% to 74.0% for TP53, from 48.4% to 75.7% for ASXL1, and from 84.4% to 93.4% for FLT3-ITD. SF3B1 was tested in 14.6% of pts with MDS and 12.0% of pts with AML; testing increased from 5.0% to 23.3% in pts with MDS and from 6.2% to 16.9% in pts with AML when comparing pts enrolled before January 1, 2017 and pts enrolled from January 1, 2017 onward. Factors associated with increased testing were age < 80 years vs ≥ 80 years (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.2–2.5; P < 0.01), enrollment at an AC site vs CO/GOV site (OR 1.7, 95% CI 1.2–2.6; P < 0.01), and geographic region outside the Midwest (OR 1.5, 95% CI 1.1–2.1; P = 0.015) in pts with MDS and age < 75 years vs ≥ 75 years (OR 2.1, 95% CI 1.3–3.6; P < 0.01) and ELN score of Favorable/Intermediate (Int)-1 vs Int-2/Adverse (OR 7.9, 95% CI 3.6–17.7; P < 0.01) in pts with AML.

Conclusions: Molecular diagnostic testing rates increased in daily clinical practice in the Connect^® MDS/AML Registry after the publication of the WHO 2016 criteria, including for SF3B1. However, rates remained lower for pts with MDS than pts with AML. This may reflect the lack of targeted therapies for MDS, although select mutations have important prognostic value in MDS. Elderly pts (MDS: ≥ 80 years; AML: ≥ 75 years) had lower rates of molecular testing than younger patients. Further education may be required to ensure that all pts who would benefit should undergo molecular testing.