Treatment Patterns and Outcomes of Patients with Primary or Secondary Acute Myeloid Leukemia By Type of Site (Academic or Community/Government): A CONNECT (R) Myeloid Registry Study

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

11-15-2022

Journal Title

Blood

Department

Medicine

Abstract

Introduction Up to 30% of acute myeloid leukemias (AML) evolve from prior hematologic disorders and are classified as secondary AML. Secondary AML is traditionally associated with worse prognosis than de novo, or primary, AML, resulting in inferior response rates and poorer survival. The treatment landscape for AML has evolved recently with the introduction of venetoclax (VEN) and the availability of targeted agents. To better understand evolution of the management of secondary AML, we evaluated treatment patterns and outcomes in patients (pts) with primary AML vs secondary AML treated in real-world clinical practice and enrolled in the CONNECT® Myeloid Disease Registry (NCT01688011) by type of site (academic or community/government).

Methods Pts were classified as having either primary or secondary AML based on history of myelodysplastic syndrome (MDS) or progression from MDS to AML. Overall survival (OS) from the date of AML diagnosis, estimated by the Kaplan-Meier method, was evaluated in each group according to type of site (academic or community/government), utilization of allogeneic hematopoietic stem cell transplantation (alloHSCT), and tumor protein p53 (TP53) mutational status. Time to adoption of a VEN-based therapy, defined as first use of VEN-based therapy following Food and Drug Administration (FDA) approval in this setting, was evaluated using a Cox model with factors for age (< 75 and ≥ 75 y), type of site, and geographic region.

Results A total of 891 pts in the Registry with a diagnosis of AML were assessed (primary AML, n = 676; secondary AML, n = 215). Median (range) ages were 70 (55-97) y in the primary AML group and 74 (19-93) y in the secondary AML group. Most pts were male (primary AML, 61.6%; secondary AML, 61.5%) and most were treated at community or government centers (primary AML, 60.2%; secondary AML, 66.0%). Pts with primary AML had significantly longer survival than pts with secondary AML; median OS (95% confidence interval [CI]) was 15.6 (13.6-17.4) mo and 5.1 (3.6-6.7) mo, respectively (P < 0.001). Median OS for pts with primary AML and secondary AML treated at academic centers was 17.0 mo and 5.6 mo, respectively (hazard ratio [HR] [95% CI], 0.41 [0.30-0.54], P < 0.001) and in community/government centers was 14.1 mo and 5.2 mo, respectively (HR [95% CI], 0.53 [0.43-0.66], P < 0.001). There was no significant difference in median OS in pts treated at academic centers compared with pts treated at community/government centers for both primary AML (academic vs community/government centers: 17.0 mo [95% CI, 14.7-20.7] vs 14.1 mo [11.0-16.9]; Figure 1A) and secondary AML (5.0 mo [95% CI, 3.0-7.2] vs 5.1 mo [3.7-7.3]; Figure 1B). Significantly longer median OS in pts with primary AML vs secondary AML was observed regardless of alloHSCT status (no alloHSCT: 11.7 mo vs 4.5 mo; HR [95% CI], 0.53 [0.44-0.64], P < 0.001; with alloHSCT: 64.3 mo [35.8-NC] vs 24.9 mo [6.8-48.9], P = 0.002]. Longer median OS was observed among pts who received alloHSCT compared with those without alloHSCT: primary AML, 41.1 mo vs 12.8 mo; secondary AML, 24.9 mo vs 4.4 mo; additional analyses are warranted to account for immortal time bias. Regardless of TP53 mutation status, pts with primary AML had significantly longer median OS than pts with secondary AML (no mutation: 22.0 mo [17.6-26.1] vs 6.2 mo [2.5-12.6], P < 0.001; with mutation: 8.8 mo [3.9-14.2] vs 3.8 mo [1.4-6.8], P = 0.014). VEN-based therapies were adopted more quickly by pts aged ≥ 75 y vs < 75 y (P < 0.001) and those treated at community or government centers vs academic centers (P = 0.045); no association between geographic region and time to adoption of VEN-based therapies was observed.

Conclusions Overall, outcomes of pts with AML in the CONNECT® Myeloid Disease Registry are consistent with previously reported outcomes. Median OS is longer in primary AML vs secondary AML regardless of whether pts receive alloHSCT or have mutations in TP53. This analysis suggests that contrary to commonly held perceptions, site of care does not affect overall pt outcome and that VEN adoption occurs sooner at community centers. The clinically meaningful increase in OS in pts receiving alloHSCT, when compared with pts without alloHSCT, regardless of primary or secondary AML further emphasizes the importance of providing pts with the opportunity for transplant. These observations merit further study into potential differences in treatment patterns and outcomes.

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