Core Binding Factor Acute Myeloid Leukemia of the Elderly Treated with Conventional Chemotherapy: A Collaborative Study of the French CBF AML Intergroup
Authors: Prebet Thomas , Boissel Nicolas , Recher Christian , Thomas Xavier , Delaunay Jacques , Cahn Jean-Yves , Pigneux Arnaud , Quesnel Bruno , Witz Francis , Thépot Sylvain , Ugo Valérie , Terre Christine , Tavernier Emmanuelle , Castaigne Sylvie , Guilhot Francois , Dombret Hervé , Vey Norbert 
Published: April 2020

Acute Myeloid Leukemia with rearrangements of CBFα or β (CBF-AML) are associated with a younger age and with a good prognosis when treated with intensive chemotherapy. CBF are infrequent in elderly patients (Appelbaum BJH 2006) and are associated with a better outcome as compared to other AMLs. Complete Remission (CR) rate and Event Free Survival (EFS) seemed to be lower than what was observed for younger patients. However, only limited data are available on the characteristics and outcome of CBF-AML in the elderly. We presents the results of a retrospective analysis of 150 patients with t(8;21) or inv(16) older than 60 years who received conventional induction chemotherapy in 17 centres of the french CBF AML intergroup (GOELAMS/ALFA groups). All patients received conventional anthracyclin + cytarabine induction therapy. Post-remission therapy consisted of low dose maintenance chemotherapy (87 patients 58%), intermediate or high dose cytarabine (47 patients, 31%) or Melphalan with autologous (SCT: 9 patients 6%). Median age was 67 years (range 60–82y). Inv(16) was found in 88 pts (58%) and t(8;21) in 62pts (42%). Additionnal chromosomal abnormalities were identified in 66 patients (44%) including 16 with trisomy 22 (11%) only in pts with Inv(16), 19 (13%) with loss of sex chromosome and 7 (5%) with del 9q mostly found in t(8;21). 132 patients achieved CR after 1 or 2 induction courses (88% CR rate), 3 pts had refractory diseasea and 15 died early (10%). 17 pts (11%) required ICU transfer during induction. Induction mortality was significantly related to poor performance status (p&lt;0.001) and High WBC count at diagnosis(p=0.015). With a median follow-up of 17 months, Overall Survival (OS) and EFS were respectively 24 and 19 months. By multivariate analysis of factors influencing OS and LFS are presented in the Table. Outcome was favorable for Inv(16) patients (OS=27 months, EFS=22 months) compared to t(8;21) patients (OS=21 months, EFS=14 months). Interestingly, the benefit of intensive consolidation was limited to t(8;21) AML (EFS NR vs 11 months, p=0.002). No impact of age as a continuous variable could be demonstrated. After relapse, Median Overall survival was 5 months with a significantly better outcome in Inv(16) patients and if relapse was delayed (more than 12 months after CR1). No impact of age on outcome after relapse could be demonstrated. This large series of elderly patients with CBF-AML show that these patients must be offered standard induction which leads to high CR rate whatever the age. Nevertheless, the majority of them relapse with conventional post-remission treatment and the impact of intensive chemo seems limited. Alternative strategies of post-remission therapy are thus warranted including new cytotoxic drugs as well as targeted molecules.

Variable RR Overall survival p= RR Event Free Survival p= High WBC count 2.56 [1.464–4.491] 0.001 2 [1.104–3.562] 0.022 ECOG (0–1 vs 2–4) 5.12 [2.878–9.112] &lt; 0.001 2.76 [1.457–5.215] 0.002 Deletion 9q 5.06 [2.125–12.05] &lt; 0.001 3.32 [1.445–7.629] 0.005 ICU admittance during induction 5.18 [2.744–9.764] &lt; 0.001 2.86 [1.216–6.717] 0.016 use of High Dose Cytarabine 0.373 [0.196–0.708] 0.003 NS NS