Outcome of Adult AML at First Relapse Following a Risk-Oriented Strategy: The Northern Italy Leukemia Group (NILG) Experience.
Authors: Cavattoni Irene M. , Morello Enrico , Mian Michael , Oldani Elena , Intermesoli Tamara , Borlenghi Erika , Rossi Giuseppe , Minotto Claudia , Terruzzi Elisabetta , Pogliani Enrico Maria , Audisio Ernesta , Marmont Filippo , Rambaldi Alessandro , Bassan Renato , Cortelazzo Sergio 
Published: October 2019

INTRODUCTION We retrospectively analyzed the impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) in 145 patients (pts) with non-APL AML who had been initially treated with standard induction and risk-adapted consolidation. The aim was to identify factors associated with a better outcome at first relapse.

METHODS All pts were at first recurrence following consolidation of CR1 with (i) high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinico-cytogenetic criteria) or (ii) allo-SCT in case of high-risk prognostic profile. Median pt age was 55 y (range 21–68). CR1 duration was ≤ 6 months in 49 pts (34%), ranging from 0.6 to 6 mo (median 3.7). 25/68 pts (37%) had an unfavourable cytogenetics (CG), and 8.2 % had MDS-related AML. 96 pts (66%) had received HiDAC and 21 (15%) an allo-SCT according to study design.

RESULTS 105 pts (72%) received salvage chemotherapy, 10 pts (7%) underwent directly allo-SCT, while the remaining 30 (21%) received palliation and all of them died. Salvage therapy consisted again of HiDAC alone or in combination with fludarabine or anthracyclines. After reinduction, 52/105 pts (49.5%) achieved CR2 and 15 (14%) died of complications. Altogether, 42 pts (29%, group 1) received an allo-SCT following relapse, 27 (64%) in CR2, 5 beyond CR2 and 10 soon after relapse. Of 20 more pts (14%, group 2) in CR2 but without HLA identical donor, 13 could be given further intensive consolidation therapy. Both groups were comparable regarding adverse prognostic features such as age >55 y, WBC count>50,000/μL, unfavourable CG, presence of FLT-3 ITD, prior allo-SCT and 1st CR lasting ≤ 6 mo. At the end of treatment, 37/42 pts (88%) receiving SCT and all 20 pts (100%) given only chemotherapy were in CR2. Logistic regression analysis showed that intensive treatment without HiDAC at induction (p=0.04) as well as CR1 lasting <6 mo (p=0.01) negatively affected CR2 rate. Median duration of CR2 was 7.5 mo (range 1–49) in group 1 compared to 4 mo (range 1–15) in group 2. Day 100 non-relapse mortality in the 2 groups was 7% and 10%. After a median follow-up of 9.4 mo in group 1 (range 3–49) and 10 mo in group 2 (range 2–65), 2-y OS was 24% and 15.5%, respectively. Notably, 2-y OS in allo-SCT group ranged from 42% in pts ≤ 45 years to 14% in older ones. Moreover, survival was affected by risk category. In fact 2-y OS of 14/37 (38%) standard risk pts undergoing allo-SCT at salvage was 41% vs 17% in 28/108 (26%) comparable high risk pts. Cox regression analysis revealed achievement of CR2 being the only independent prognostic factor related to overall survival (p=0.0001).

CONCLUSIONS AML patients receiving intensive chemotherapy including HiDAC at 1st relapse reached a high CR2 rate, regardless of type of prior risk-adapted consolidation. Further intensification with allo-SCT may offer substantial salvage rates to younger standard risk patients, thus adding value to the underlying concept of a risk-oriented first-line therapy.