Real‐world data on treatment patterns and outcomes of hypomethylating therapy in patients with newly diagnosed acute myeloid leukaemia aged ≥ 60 years

Österroos, Albin; Eriksson, Anna; Antunović, Petar; Cammenga, Jörg; Deneberg, Stefan; Lazarević, Vladimir; Lorenz, Fryderyk; Möllgård, Lars; Derolf, Åsa Rangert; Uggla, Bertil; Wennström, Lovisa; Ölander, Emma; Höglund, Martin; Juliusson, Gunnar; Lehmann, Sören

doi:10.1111/bjh.16410

Cited by 13 publications

(18 citation statements)

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“…Overall survival was comparable amongst patients preselected to receive induction chemotherapy regardless of subsequent randomization. These results are in accord with a retrospective study that demonstrated similar survival between elderly AML patients treated with intensive induction chemotherapy versus HMA, and Swedish retrospective registry-based study [44,45]. DACO-016 study was implemented in a similar fashion, randomizing patients between 5 days of standard-dose decitabine every 4 weeks and treatment choice (TC), which included LDAC or supportive care (SC).…”

Section: Nonintensive Therapysupporting

confidence: 76%

“…(d) Comparison of OS between HMA and PC in PSM groups within the cytogenetic risk groups. For all survival analyses, patients who underwent allogeneic transplantation were censored at the date of transplantation [44].…”

Section: Discussionmentioning

confidence: 99%

“…Older adults with AML often have high‐risk cytogenetic and molecular features conferring chemoresistance, and poor functional status leading to increased treatment intolerance; hence, survival of older adults has largely remained unchanged in the last few decades [84]. Data from the recent ‘real‐life’ population‐based study from Sweden show that HMA treatment results were similar to intensive chemotherapy in patients aged ≥60 years in terms of OS using multivariate analysis, as well as in a propensity score matching analysis, whilst there was a clear benefit of HMA compared with palliative treatment (Figure 2a‐d) [44]. After a long time of having a relatively simple ‘one‐size‐fits‐all’ 3 + 7 approach followed by consolidation (with or without allo‐SCT), we are now sailing into the age of more genetically directed therapy, where understanding genetic landscape at diagnosis may dictate quite differing treatment options.…”

Section: Discussionmentioning

confidence: 99%

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Acute myeloid leukaemia in patients we judge as being older and/or unfit

Lazarevic

2021

J Intern Med

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Section: Nonintensive Therapysupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Acute myeloid leukaemia in patients we judge as being older and/or unfit

Lazarevic

2021

J Intern Med

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“…Conversely, two recent analyses of elderly patients (≥65 years) with AML in Korea noted that despite lower response rates in patients who received HMAs compared with those who received ICT, survival outcomes were comparable [35, 36]. Other studies involving elderly patients with AML have also reported comparable or better survival outcomes for those who received HMAs compared with those who received ICT or palliative care [37]. Notably, there were patients in this subanalysis who received only palliative BSC despite the availability of first-line systemic therapies.…”

Section: Discussionmentioning

confidence: 99%

Real-world treatment patterns and clinical outcomes in Korean patients with AML ineligible for first-line intensive chemotherapy: A subanalysis of the CURRENT study, a non-interventional, retrospective chart review

Bang

Kang

Song

et al. 2022

Preprint

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Background Although most elderly patients with acute myeloid leukemia are ineligible for intensive chemotherapy, treatment options remain limited. CURRENT (UMIN000037786), a real-world, non-interventional, retrospective chart review, evaluated clinical outcomes, clinicopathologic characteristics, and treatment patterns in these patients. We present results from a subanalysis of Korean patients in this study. Methods Patients were aged >=18 years with primary or secondary acute myeloid leukemia ineligible for intensive chemotherapy who initiated first-line systemic therapy or best supportive care between 2015 and 2018 across four centers in Korea. Primary endpoint was overall survival from diagnosis. Secondary endpoints included progression-free survival, time to treatment failure, and response rates. Data analyses were primarily descriptive, with time-to-event outcomes estimated using the Kaplan-Meier method, and Cox regression used to determine prognostic factors for survival. Results Among 194 patients enrolled, 84.0% received systemic therapy and 16.0% received best supportive care. Median age at diagnosis was 74 and 78 years, and Eastern Cooperative Oncology Group performance status 0 or 1 was reported in 73.0% and 48.4% of patients, respectively; poor cytogenetic risk was reported in 30.1% and 16.1% of patients. Median overall survival was 7.83 versus 4.50 months, and median progression-free survival was 6.73 versus 4.50 months in the systemic therapy versus best supportive care groups. Prognostic factors (all P <0.05) affecting overall survival included secondary acute myeloid leukemia (hazard ratio, 1.67 [95% CI: 1.13–2.45]), Eastern Cooperative Oncology Group performance status >=2 (2.41 [1.51–3.83]), poor cytogenetic risk (2.10 [1.36–3.24]), and Charlson comorbidity index >=1 (2.26 [1.43–3.58]). Conclusion Clinical outcomes are poor in Korean patients with acute myeloid leukemia ineligible for intensive chemotherapy who are prescribed current systemic therapies or best supportive care. There is a substantial unmet need for novel agents (monotherapy or in combination) to improve clinical outcomes in this patient population.

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“…Comparisons between intensively and palliatively treated patients are included in Table 1, Supplementary Table S1 and Table S2. Only patients with palliative and intensive treatment are further described related to CR and OS due to the low number of HMA-treated patients since HMAs were not widely used in Sweden during the inclusion period 16 .…”

Section: Patient Characteristics and Outcomementioning

confidence: 99%

Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia

et al. 2020

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Relevant molecular tools for treatment stratification of patients ≥65 years with acute myeloid leukemia (AML) are lacking. We combined clinical data with targeted DNA-and full RNA-sequencing of 182 intensively and palliatively treated patients to predict complete remission (CR) and survival in AML patients ≥65 years. Intensively treated patients with NPM1 and IDH2 R172 mutations had longer overall survival (OS), whereas mutated TP53 conferred lower CR rates and shorter OS. FLT3-ITD and TP53 mutations predicted worse OS in palliatively treated patients. Gene expression levels most predictive of CR were combined with somatic mutations for an integrated risk stratification that we externally validated using the beatAML cohort. We defined a high-risk group with a CR rate of 20% in patients with mutated TP53, compared to 97% CR in low-risk patients defined by high expression of ZBTB7A and EEPD1 without TP53 mutations. Patients without these criteria had a CR rate of 54% (intermediate risk). The difference in CR rates translated into significant OS differences that outperformed ELN stratification for OS prediction. The results suggest that an integrated molecular risk stratification can improve prediction of CR and OS and could be used to guide treatment in elderly AML patients.

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Real‐world data on treatment patterns and outcomes of hypomethylating therapy in patients with newly diagnosed acute myeloid leukaemia aged ≥ 60 years

Cited by 13 publications

References 9 publications

Acute myeloid leukaemia in patients we judge as being older and/or unfit

Acute myeloid leukaemia in patients we judge as being older and/or unfit

Real-world treatment patterns and clinical outcomes in Korean patients with AML ineligible for first-line intensive chemotherapy: A subanalysis of the CURRENT study, a non-interventional, retrospective chart review

Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia

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