Real life experience with frontline azacitidine in a large series of older adults with acute myeloid leukemia stratified by MRC/LRF score: results from the expanded international E-ALMA series (E-ALMA+)

Falantes, José; Pleyer, Lisa; Thépot, Sylvain; Almeida, António; Maurillo, Luca; Martínez-Robles, Violeta; Stauder, Reinhard; Itzykson, Raphaël; Pinto, Roberto; Venditti, Adriano; Bargay, Joan; Burgstaller, Sonja; Martínez, María Pilar; Seegers, Valérie; Cortesão, Emília; Foncillas, María Ángeles; Gardin, Claude; Montesinos, Pau; Musto, Pellegrino; Fenaux, Pierre; Greil, Richard; Sanz, Miguel Á.; Ramos, Fernando

doi:10.1080/10428194.2017.1365854

Cited by 25 publications

(29 citation statements)

References 34 publications

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“…30 Gupta et al found no association between WBC at diagnosis and survival, while two European studies of 710 and 149 patients treated with frontline azacitidine reported an increased mortality (with HR of 1.52 and 2.38, respectively) in subjects with high WBC. [26][27][28] Our data thus add to the body of evidence supporting an unfavourable role of elevated WBC level (HR=1.12; 95% CI: 1.06-1.18).…”

Section: Discussionsupporting

confidence: 60%

“…Genetic abnormalities are recognized key factors in the prognosis of AML . Some studies examining predictors of survival in patients treated with epigenetic therapy confirmed that cytogenetics play an important role in these patients, too, though others did not confirm this finding …”

Section: Discussionmentioning

confidence: 99%

“…8 4 Some studies examining predictors of survival in patients treated with epigenetic therapy confirmed that cytogenetics play an important role in these patients, too, though others did not confirm this finding. [26][27][28][29] The prognostic role of WBC count in AML has also been documented, but information from RW studies on hypomethylating agents is scanty. 30 Gupta et al found no association between WBC at diagnosis and survival, while two European studies of 710 and 149 patients treated with frontline azacitidine reported an increased mortality (with HR of 1.52 and 2.38, respectively) in subjects with high WBC.…”

Section: Discussionmentioning

confidence: 99%

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Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Bocchia

Candoni²,

Borlenghi

et al. 2019

Hematological Oncology

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Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real‐world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient‐level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first‐line decitabine therapy at the registered schedule of 20 mg/m2/iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all‐cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy‐one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable‐intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse‐free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7‐16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13‐2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06‐1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first‐line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Bocchia

Candoni²,

Borlenghi

et al. 2019

Hematological Oncology

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“…Secondary acute myeloid leukemia (sAML) evolving from an antecedent hematological disorder and therapy‐related sAML represent high‐risk subsets of AML and are associated with poor clinical outcome . The hypomethylating agents (HMA), azacitidine, and decitabine represent treatment options for elderly AML patients including sAML patients unfit for intensive chemotherapy . Treatment options after HMA failure usually consist of BSC or low‐dose cytarabine, and the prognosis remains limited with a median OS of 3.4 months .…”

Section: Introductionmentioning

confidence: 99%

“…1 The hypomethylating agents (HMA), azacitidine, and decitabine represent treatment options for elderly AML patients including sAML patients unfit for intensive chemotherapy. [2][3][4][5] Treatment options after HMA failure usually consist of BSC or lowdose cytarabine, and the prognosis remains limited with a median OS of 3.4 months. 6 Therefore, there is a high clinical demand for new therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL‐2 and/or BIM

Huemer

Melchardt

Jansko

et al. 2019

European J of Haematology

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Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL‐2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL‐2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non‐responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.

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A phase 3 trial of azacitidine versus a semi‐intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia

Vives

Martínez‐Cuadrón²,

Burgues

et al. 2021

Cancer

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BACKGROUND: Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA). METHODS: Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase. RESULTS: The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001). CONCLUSIONS: FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.

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Real life experience with frontline azacitidine in a large series of older adults with acute myeloid leukemia stratified by MRC/LRF score: results from the expanded international E-ALMA series (E-ALMA+)

Cited by 25 publications

References 34 publications

Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL‐2 and/or BIM

A phase 3 trial of azacitidine versus a semi‐intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia

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