Azacitidine, intensive chemotherapy or best supportive care in relapsed or refractory acute myeloid leukemia, a DATAML registry study

2022 ◽  
pp. 1-9
Author(s):  
Noémie Gadaud ◽  
Harmony Leroy ◽  
Emilie Bérard ◽  
Suzanne Tavitian ◽  
Thibaut Leguay ◽  
...  
2015 ◽  
Vol 56 (8) ◽  
pp. 2326-2330 ◽  
Author(s):  
Sylvain P. Chantepie ◽  
Emilie Reboursiere ◽  
Jean-Baptiste Mear ◽  
Anne-Claire Gac ◽  
Veronique Salaun ◽  
...  

2014 ◽  
Vol 89 (12) ◽  
pp. E244-E252 ◽  
Author(s):  
Pierre Bories ◽  
Sarah Bertoli ◽  
Emilie Bérard ◽  
Julie Laurent ◽  
Eliane Duchayne ◽  
...  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3582-3582
Author(s):  
Osamu Imataki ◽  
Hiroaki Ohnishi ◽  
Yasunori Kawachi ◽  
Makoto Ide ◽  
Makiko Uemura ◽  
...  

Abstract Abstract 3582 Background: Japan is one of the prominent aging countries, in where incidence and mortality of malignancy in elderly is increasing which is recognized as a concerned national health care issue. Among various types of cancer, incidence and prevalence of elderly acute myeloid leukemia (AML) is increasing as well, and in the most cases those patients have concomitant diseases. Thus far, the treatment for AML in elderly has been generally realized to reduce the dose intensity due to impaired organ function and comorbidity. However, the utility of dose reduction in elderly AML has not been well understood. Thereby, we performed a retrospective population cohort study of AML in a local community in Japan in order to investigate practical risk factor based on general patient population including more than 65 to 75 years old. Patients and method: We reviewed medical charts and medical records of AML patients diagnosed at seven institutions in Kagawa prefecture between January 1, 2006 and December 31, 2010. We collected patients' characteristics, background, and clinical information including laboratory data, adverse events and outcome. Induction therapy regimen was practically decided by each treating physician based on available clinical data and local standards of care, but not on karyotype. We categorized chemotherapy regimens for non-APL patients into 3 groups; intensive chemotherapy, less-intensive chemotherapy, or best supportive care. Results: A total of 213 patients (127 males and 86 females) were diagnosed with AML. With an average population during study periods in Kagawa, the incidence of AML is 4.26 per 100,000 per year. The male to female ratio was 1.48. The median age was 70 years (average 67, range 24∼95). There were 16 APL patients and 197 non-APL patients in this cohort. The 5-year overall survival (OS) rate was 21.1%. In patients who are likely to meet criteria usually applied in clinical studies (i.e., de novo AML with PS 0 to 2 and no renal dysfunction), the 5-year OS rate was 31.5%. Among 197 non-APL patients median age was 70 years (range 24∼95) consists of 119 males and 78 females. The chromosomal karyotype is known to be the strongest prognostic predictor, and each study group advocates the different classification. We classified our cohort according to 5 different karyotype classifications (NCCN, BSCH, MRC-AML10, SWOG and CALGB). On the whole, 4.4∼5.9% of the patients were classified as having favorable risk karyotypes, and 17.7∼29.1% of the patients had unfavorable risk karyotypes. In terms of treatment intensity, 51.8% patients (102/197) received intensive induction chemotherapy. A majority (71.6 %) of patients ≤ 64 years were treated with intensive chemotherapy, while approximately half (46.0%) of patients aged 65 to 74 years, and only 35.6% of patients ≥ 75 years received intensive chemotherapy as induction therapy (P < 0.001). A complete remission (CR) rate in patients treated was 67.6% (69/102) with intensive regimen, 30.4% (17/56) with less-intensive regimen, and 0.0% (0/39) with best supportive care (P < 0.001). Eight week mortality was 6.9% (7/102), 19.6% (11/56), and 41.0% (16/39), respectively (P < 0.001). In non-APL patients, the 5-year OS rate was 10.6%. Subsequent analysis by age group showed that the 5-year OS rate declined with age; the 5-year OS rate and the median survival of non-APL patients ≤ 64 years, 65∼74 years, and ≥ 75 years were 41.5% and 19 months, 14.1% and 10 months, and 8.9% and 7 months, respectively (P = 0.003). Multivariate analysis revealed aging older than 65 year-old, best supportive care, poor PS more than 3, antecedent hematological disease, and unfavorable risk karyotypes were independent adverse prognostic factors associated with OS. Discussion: This analysis provides virtual data from an unselected AML population in a Japanese cohort. Our data can be applied for realistic risk assessment for AML patients including elderly. The present result indicates all prognostic factors has comparable impact on survival, therefore chemotherapy can compensate other adverse prognostic factors even in an elderly patient with poor PS. In aggregates, we conclude it is the best way to adapt as intensive chemotherapy as possible to improve outcomes in the treatment of elderly AML. In further investigation, the external validity of the risk assessment based on identified prognostic predictors from our cohort should be reevaluated for a third party cohort from other countries. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Marta Riva ◽  
Lorenzo Rizzo ◽  
Valentina Mancini ◽  
Rosa Greco ◽  
Giambattista Bertani ◽  
...  

Background: The treatment for relapsed or refractory acute myeloid leukemia (R/R AML) has minimal chances and a low impact on improving survival. One of the most important goal is to treat unfit patients who are often intolerant to intensive chemotherapy and are not eligible for allogeneic stem cell transplantation. Most patients with AML, including nearly all patients older than 60 years, present multiple, sequentially acquired, somatic mutations. Isocitrate dehydrogenase 2 (IDH2) mutations are present in approximately 8-19% of cases (Buege MJ, Cancers 2018). IDH2 mutations occur early in the leukemogenesis and accumulate an oncogenic product (R-2-hydroxyglutarate) that arrests the histone demethylation pathway, thereby stopping haematopoietic differentiation (Rakheja D, Hum Pathol. 2012). Enasidenib (ENA) is a selective, powerful oral inhibitor of the oncogenic activity of the IDH2 mutant enzyme, that decreases R-2-hydroxyglutarate levels in vitro and in vivo. Interestingly, phase I/II trials showed an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of complete remission (CR) and with 6.8 % of CR with incomplete haematological recovery (CRi). Moreover, the reported median overall survival was 9.3 months, with 19.7 months (mo) for patients who achieved CR (Stein E, Blood 2017). Aims: To study retrospectively the efficacy and safety of ENA, as single agent, in improving overall survival (OS) and progression-free survival (PFS) in IDH2 mutated R/R AML patients (pts), unfit for intensive chemotherapy. Furthermore, to compare outcomes with a cohort of patients with R/R AML IDH2 wild-type (wt). Methods: Since 2018 we have retrospectively collected and analyzed data of unfit IDH2 mutated R/R AML patients, treated with ENA, thanks to the expanded access program of this drug. The dose was 100 mg/day for all pts. PFS and OS were estimated using the Kaplan-Meier product limit method. Therefore, we considered, as historical comparison, a sample of 28 pts with R/R IDH2 wt AML, treated with the best available therapy at our Institution in the same time frame and matched for clinical features. OS and PFS were compared using the log-rank test. Results: Nine IDH2 mutated pts were considered for analysis: 4 (44%) cases were de novo AML, while 5 (56%) were secondary (1 myelodysplasia and 4 myeloproliferative neoplasms). Median age at relapse was 71 years (range 47-79). Median number of previous therapies was 2 (range 1-3). All pts completed at least one cycle of ENA with a median number of 5 cycles (range 1-16). Median OS from AML diagnosis and from the beginning of ENA was 28 mo (range 3-65), and 15 mo (range 1-27) respectively; median PFS was 13 mo (range 1-14). Among the 28 patients of the control group, with a median age at relapse of 74 years (range 65-86) we recorded a median OS of 14 mo (range 7-62) and an OS from the last relapse of 2 mo (range 0,5-26). The ENA pts group showed a significantly better OS than the control population (p = 0,0419) (Figure 1). The most prominent toxicities were hyperbilirubinemia in 2 pts (22,2%) and IDH-differentiation syndrome (IDH-DS) in 3 (33,3%); though the drug was generally well tolerated. Therefore, patients were treated as outpatients in most cases. Conclusions: In the era of precision medicine, molecular target therapy is the most promising strategy to increase the probability of treatment success with limited side effects. Our experience confirms the efficacy of the IDH2 inhibitor ENA to treat unfit patients with R/R AML in the real life, showing significantly better outcome in terms of survival for the pts treated with target therapy, compared to pts treated with standard therapy. Disclosures Veronese: Janssen Cilag:Honoraria;Bayer:Honoraria;Novartis:Other: Travel Expenses;AstraZeneca:Other: Travel Expenses.


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