AML is a disease of older adults, with an average age at diagnosis of 67. Patients with high risk disease considered unfit for induction chemotherapy are often candidates for hypomethylating agents (HMA), namely azacitidine and decitabine. These agents have shown promise in this population, with several trials demonstrating a benefit to overall survival compared to best supportive care alone. Yet the healthcare consumption associated with HMA therapy is less clear. HMAs are thought to be well tolerated, with significantly less non-hematological side effects compared to intensive induction therapy. However, the non-medical burden-primarily social and economic- due to these agents and associated toxicities has yet to be compared to intensive induction therapy.
We queried 492 patients at our institution between 2010-2016 with a new diagnosis of AML. Inclusion criteria were older patients (age >65) with cytogenetically high risk AML treated with either HMAs or intensive induction. 84 patients fit the inclusion criteria for this study. Patients were assessed for chemotherapy regimen at time of diagnosis, transplant free survival (TFS; defined as the time period from diagnosis to death or hematopoietic stem cell transplant (HSCT), whichever occured first), encounters in the healthcare setting (office or hospital), charges accrued until death or HSCT, blood transfusions (red blood cells and platelets) administered, and overall survival.
31 patients received HMAs and 53 underwent intensive (7+3 or equivalent) induction therapy. 30 patients underwent HSCT (HMA:7, Intensive induction: 23). Mean age was 69 years in the intensive induction arm and 73 years in the HMA arm. The groups were well matched according to treatment related mortality probability (TRM) scores (10.4% intensive induction vs. 15.4% HMA group. p-value :0.086). Median transplant free survival (TFS) was 257 days in the HMA group vs. 337 days in the intensive induction group (p-value : 0.10). The mean number of encounters with the healthcare system (inpatient and outpatient encounters) was not significantly different between HMA vs. intensive induction groups (27.3 days vs 34.9 days p-value: 0.48). Mean encounters per TFS (defined as total encounters per individual divided by the individual patient's TFS) was 28.6% in the HMA group vs. 35.5% in the intensive group. The HMA group received a mean of 24.4 transfusions vs. 19.3 in the intensive induction group (p-value : 0.25). Differences in charges per day between groups did not vary significantly, with the HMA group averaging $1202.64 per day and the intensive induction group $1051.38 per day (p-value : 0.079). Mean overall survival was 472 days in the intensive induction group without HSCT, and 1102 days with HSCT. In the HMA group, overall survival was 258 days without HSCT, and 815 days with HSCT respectively. 30 day treatment related mortality was low in both groups (HMA= 3%, Intensive induction= 5%).
Patients receiving hypomethylating agents comprise a group of patients who are traditionally thought to have a significantly less amount of healthcare consumption when compared to patients undergoing intensive induction. This data demonstrates that patients receiving HMA therapy spent nearly a third of their remaining survival in contact with the healthcare setting, whether inpatient or outpatient. This is nearly equivalent to the time spent in the healthcare setting of their disease risk matched peers undergoing intensive induction. Patients treated with HMAs also received a similar number of blood product transfusions compared to patients undergoing intensive induction. Thus, HMA therapy requires supportive care that is comparable to intensive induction amongst older patients with cytogenetically high risk AML, and is associated with nearly equivalent amounts of healthcare consumption. Given that it may take 4-6 months to see the full hematological effect with HMA therapy, this data may help better educate and guide treatment choices between the clinician and patient when deciding on therapy for older high risk AML patients.
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