Page 118 - 2018_11-Haematologica-web

V.V. Prassek et al.
risk category had significant negative impacts on OS. There was a trend towards worse OS for patients with poor ECOG PS.
Patients who were characterized by wildtype IDH1, favorable or intermediate cytogenetics and an ECOG PS of 0-2 had a significantly longer median OS than patients who had at least one high-risk feature (mutated IDH1, adverse cytogenetics, and/or performance status ≥3) (3- year OS, 25% versus 5%; P<0.001) (Figure 5).
Association between the European LeukemiaNet 2017 and Medical Research Council classifications
and outcomes
When we applied the novel ELN 2017 genetic risk clas- sification to our cohort of very old patients, more patients were assigned to the favorable- and adverse-risk cate- gories, and fewer patients to the intermediate-risk group, compared to the MRC classification (Table 1). Surprisingly, patients classified as ELN-2017 intermediate- risk had longer OS (median, 10.7 months) compared to both the favorable- and adverse-risk groups (median, 3.4 months and 3.6 months, respectively; P=0.009) (Figure 1B). Furthermore, in the MRC adverse-risk subgroup, all patients died within 2 years, whereas seven ELN-2017 adverse-risk patients survived for 3 years or longer.
A
B
Figure 4. IDH1 mutations and survival. (A) Overall survival in IDH1-mutated patients (red line) compared to IDH1-wildtype patients (green line). (B) Overall survival in NPM1-mutated/IDH1-mutated patients (red line) compared to NPM1- mutated/IDH1-wildtype patients (green line). Mut: mutated; wt: wildtype.
Discussion
Elderly AML patients are frequently underrepresented in clinical trials evaluating induction chemotherapy sched- ules, as well as in studies of the genetic basis of the dis- ease.12,28-30 For example, the widely-used MRC cytogenetic risk categories were derived from a cohort of patients aged 16-59 years.18 This selection bias contrasts with the epi- demiology of AML, which is mostly a disease of elderly patients. While many study groups have excluded older patients from trials involving induction chemotherapy, and less-intensive regimens, including the hypomethylat- ing agents, decitabine and azacitidine, are now widely used in this age group, some studies suggest that a sub- group of old patients may benefit from induction chemotherapy.7,8,10 There is, therefore, a vital need to iden- tify factors that are associated with outcomes and that could support therapeutic decision-making in this diffi- cult-to-treat patient cohort.
We designed our study to focus on a cohort of very old patients (aged 75 years or older) included in a trial of induction chemotherapy. In this age group, the benefits of induction chemotherapy and potential clinical and genetic markers for therapy success or failure are not well defined. We found that, even among very old patients, favorable-
Table 2. Multivariate analysis for overall survival.
Variable
MRC cytogenetic risk group
(adverse vs. favorable/ intermediate)
NPM1-mutated
TP53-mutated
IDH1-mutated
ECOG performance status
HR (95% CI)
2.21 (1.19 – 4.09)
0.97 (0.62 – 1.51) 1.32 (0.69 – 2.49) 3.68 (1.87 – 7.23) 1.68 (0.89 – 3.18)
P
0.012
0.889
0.402 <0.001 0.113
(3-4 vs. 0-2)
HR: hazard ratio; CI: confidence interval; MRC: British Medical Research Council;
ECOG: Eastern Cooperative Oncology Group.
Figure 5. Impact of Eastern Cooperative Oncology Group performance status, Medical Research Council classification and IDH1 mutations on overall survival. Overall survival in patients with an ECOG performance status of 0-2, favorable or intermediate MRC category and IDH1-wildtype compared to patients with an ECOG performance status of 3-4 or MRC adverse category or IDH1 mutation.
1858
haematologica | 2018; 103(11)