Real-World Treatment Patterns and Clinical Outcomes in Unfit Patients with AML Receiving First-Line Systemic Treatment or Best Supportive Care (CURRENT): Final Analysis

Background: Acute myeloid leukemia (AML) occurs mainly in older adults and is associated with poor outcomes with increasing age. Estimated 5-year survival for the overall population with AML in the US is 29% but is <10% for those aged >65 years (SEER registry, National Cancer Institute; Palmieri et al. 2020). For patients able to tolerate intensive treatment, induction chemotherapy followed by consolidation therapy is the standard of care (NCCN guidelines. 2019). However, older patients are often unable to tolerate such a regimen, which limits their treatment options and contributes to the poor prognosis of this cohort (Dombret et al. 2015). Options for patients considered unfit for intensive chemotherapy include hypomethylating agents (HMA), low-dose cytarabine (LDAC), and best supportive care (BSC), with overall survival (OS) estimates of 9.6–10.4, 4.1–6.4, and 3.6–3.7 months (mo), respectively, reported in various studies in older patients (Amadori et al. 2016; Di Nardo et al. 2020; Dombret et al. 2015; Wei et al. 2020). With an aging population and incidence of AML rising, there is a growing need to understand current treatment pathways and their respective clinical outcomes, particularly in a landscape of emerging therapies. The aim of this retrospective study was to evaluate real-world clinical outcomes in patients with AML unfit for intensive chemotherapy receiving first-line therapy or BSC.

Methods: This noninterventional, retrospective chart review was conducted across 112 centers in 22 countries. Adults with primary or secondary AML ineligible for intensive induction chemotherapy as evidenced by administration of first-line low-intensity chemotherapy, targeted therapy, or BSC were included if therapy was initiated from January 1, 2015, to December 31, 2018. Patients were followed until last recorded contact or death. Patients with an unconfirmed diagnosis, with acute promyelocytic leukemia, or who received first-line treatment in a clinical study were excluded. The primary endpoint was overall survival (OS) from diagnosis of AML. Secondary endpoints included progression-free survival (PFS), time to treatment failure (TTF), and response rates (complete remission [CR] + CR with incomplete hematologic recovery [CRi]) according to the treating physician’s assessment. Analyses are primarily descriptive, with Kaplan–Meier used to estimate time-to-event outcome measures.

Results: The final data cutoff on March 31, 2020, included 1762 patients with AML, of whom 1310 (74%) received first-line systemic therapy and 452 (26%) received BSC. Of those who received first-line therapy, 62% received HMA, 15% received LDAC, and 23% received other systemic therapies, including combination therapies. Of 1310 patients who received first-line systemic therapy, 18% received second-line active systemic therapy. Baseline characteristics were generally similar in the first-line therapy and BSC cohorts, although those who received BSC tended to be older (median age 78 vs 74 years), have a higher burden of comorbidities (85% vs 79%) and a higher Eastern Cooperative Oncology Group Performance Status (ECOG-PS ≥2 54% vs 39%). Clinicopathologic characteristics are shown in the Table. Median OS was 9.9, 7.9, and 5.4 mo for patients who received HMA, LDAC, and other systemic therapies, respectively, and 2.5 mo for patients who received BSC only. Median PFS was 4.7 mo in the overall population and 7.5, 5.3, 4.1, and 2.1 mo for those who received HMA, LDAC, other systemic therapies, or BSC only, respectively. Median TTF was 4.9, 2.1, 2.2, and 2.1 mo in those who received HMA, LDAC, other systemic therapies, or BSC only. CR/CRi was achieved by 157 patients (19%) who received HMA, 54 (27%) who received LDAC, and 64 (21%) who received other systemic therapies, with a median time to best response of 115, 55, and 41 days, respectively, and a median duration of CR/CRi/partial response of 260, 266, and 196 days, respectively.

Conclusions: Clinical outcomes for patients with AML who are ineligible for intensive chemotherapy remain poor. OS was generally consistent with clinical trials, with a median OS <10 mo for all treatment options. HMA continue to be a common treatment for this population and are associated with a modest improvement in OS and TTF relative to LDAC and BSC. Development of novel agents and combination therapies remains an unmet clinical need in unfit patients with AML.