Intensive Treatment in Elderly AML Patients Induce Prolonged Survival and Disease Remission If Early Mortality Is Prevented: The Case Record of the San Raffaele Scientific Institute
Authors: Bernardi Massimo , Carrabba Matteo , Tassara Michela , Messina Carlo , Crotta Alessandro , Sala Elisa , Vignati Alessandro , Guggiari Elena , Greco Raffaella , vago Luca , Gentner Bernhard , Piemontese Simona , Assanelli Andrea , Peccatori Jacopo , Corti Consuelo , Ciceri Fabio 
Published: October 2019

Abstract
Abstract 4583

Background:
the outcome of pts older than 65 with AML is dismal because of the unfavourable characteristics of the disease and the frequent co-morbidities. Intensive chemotherapeutic programs, with or without haematopoietic stem cells transplantation (HSCT), are not usually offered to these pts since they are considered too toxic. If treated with intensive therapeutic programs these pts show initial complete remission (CR) rates around 45% to 55% and 2 years survival of 10–20%. Since 2001 in our institution we have systematically screened AML elderly patients older than 65 yrs for comorbidites and offered to “fit” AML elderly pts an intensive approach aimed at curing the disease. In this single-center retrospective study we describe the outcome of this court of pts.

Aim:
to evaluate toxicity and survival after intensive treatments in an homogeneous court of AML pts older than 65.

Methods:
from 10/2001 to 3/2011 we treated 60 pts older than 65, median age 70 (66–77), 30 pts ≤70 yrs (median 68, 66–70), and 30 pts >70 (median 73, 71–77). Among AML pts older than 65 years old we considered eligible for intensive chemotherapy those with PS (ECOG) ≤ 2, renal, hepatic and cardiac function parameters within normal ranges. All pts signed informed consent for intensive chemotherapy. Diagnosis (WHO): 33 AML with MDS related changes, 4 AML with minimal differentiation, 6 AML w/o maturation, 8 AML with maturation, 5 AMML, 1 erythrolaeukemia, 1 AML with mutated NPM1, 2 t-AML. Cytogenetics: 43 intermediate risk (33 with normal karytotype), 10 high risk (7 complex, 3 with Monosomal Karyotype), 2 good risk, 5 not evaluable. Induction with one or two of the following chemo cycles was administered to each patient: FLAG-IDA (fludarabine + cytarabine + idarubicin) or 3–7 (cytarabine + daunorubicin, idarubicin or mitoxantrone), high-dose cytarabine (HiDAC). Post-remission treatment: chemotherapy (CHT) 1 patient, HiDAC 12 pts, autologous transplantation (AUTO) 14 pts, allogeneic transplantation (ALLO) 2 pts.

Results:
overall induction related mortality was 18.3%, 7% in pts ≤70 yrs, 30% in 30 pts >70 p=0.041, CR rate was 57% (34 pts), 73% in pts ≤70 yrs, 40% in pts >70 p=0.018. Relapse rate was 73.5% (25 pts), 68% pts ≤70 yrs, 83% in pts >70. Median OS was 386 days, 2 and 5 yrs OS was 38 and 19%, respectively, median DFS was 397 days and 2 yrs DFS was 22%. In pts ≤70 and >70 yrs, median OS and DFS were 574 and 313, 397 and 425 days, respectively, p=ns, 2 and 5 yrs OS was 41% and 27%, 30% and 8%, 2 yrs DFS 27% and 17%, respectively, p=ns. OS of pts who obtained the CR after induction: median 1155 and 790 days for pts ≤70 and >70 yrs, respectively, p=ns, 2 yrs OS 51% and 58%, respectively, p=ns.

Conclusions:
our data suggest that prolonged survival can be achieved in elderly AML who are fit to receive intensive chemotherapy. Data on mortality and remission induction are very promising in pts 66–70 yrs old, whereas early death is an important cause of treatment failure in older pts (>70), together with disease relapse. However, also older pts, with a median age of 73, who obtain the CR can reach a survival plateau at 2 yrs. Overall, these results i) indicate that selection of elderly AML pts for treatment assignment should be refined by the development of new tools for oncologic-geriatric assessment rather than by PS and vital organ function evaluation ii) prompt to design of prospective trials addressing the role of intensive regimens and transplantation programs in “fit” elderly AML pts.

Disclosures:
No relevant conflicts of interest to declare.