A scoring system for AML patients aged 70 years or older, eligible for intensive chemotherapy: a study based on a large European data set using the DATAML, SAL, and PETHEMA registries.

In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3-12% (n = 226, 41%; median OS = 9 months) and <3% (n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.

Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries.

The outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7-11.6) and 9.2 months (95% CI: 8.3-10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P < 0.0001). Treatment effect on overall survival was time-dependent. The Royston and Parmar model showed that patients treated with hypomethylating agents had a significantly lower risk of death before 1.5 months of follow-up; no significant difference between 1.5 and 4.0 months, whereas patients treated with intensive chemotherapy had a significantly better overall survival from four months after start of therapy. This study shows that intensive chemotherapy remains a valuable option associated with a better long-term survival in older AML patients.

Venetoclax combination therapy with hypomethylating agents in young adults with relapsed/refractory acute myeloid leukaemia.

In recent years, one of the most successful advances in treating acute myeloid leukaemia (AML) has been the combination of the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax with hypomethylating agents (decitabine or azacytidine). This combination treatment has an accelerated approval by the Food and Drug Administration for newly diagnosed AML adults who are 75 years of age or older or who have comorbidities and are not eligible to receive intensive induction chemotherapy. AML is the most common form of acute leukaemia in adults, with a median age at diagnosis of 68 years. Consequently, most of the patients included in the studies are elderly. Traditionally, young patients achieve higher remission rates compared with the elderly AML population. Although venetoclax combination therapy could become a treatment option for treating young patients with relapsed/refractory AML, this regimen has not been systematically tested in this setting. In this study, we summarize the currently available evidence on the treatment of venetoclax in combination with hypomethylating agents for the treatment of young relapsed/refractory AML patients, in addition to our experience in clinical practice with two case reports. Venetoclax, combined with hypomethylating agents, seems to be an effective option for young relapsed/refractory AML patients. However, due to the poor quality of the evidence, additional well-designed studies with greater numbers of patients are needed to confirm the effectiveness and safety of venetoclax combination regimens for this population.