PF257 GEMTUZUMAB OZOGAMICIN COMBINED WITH CYTARABINE FOR ACUTE MYELOID LEUKEMIA PATIENTS IN FIRST RELAPSE
Authors: Fourmont A.‐M. , Rabian F. , Raffoux E. , Ades L. , Lengline E. , Peffault de la Tour R. , Dhedin N. , Mathis S. , Cuccuini W. , Maarek O. , Clappier E. , Fenaux P. , Itzykson R. , Dombret H. , Boissel N. 
Published: June 2019

Background:Although the majority of adult acute myeloid leukemia (AML) patients achieve complete remission (CR), a relapse still occurs in 35–80% of cases mostly depending on baseline clinical and cytogenetic characteristics. The prognosis of patients with AML relapse remains very poor with 10–20% long‐term survival rates. At relapse, the common admitted strategy is to reach a second CR (CR2) and to bridge eligible patients to allogeneic hematopoietic stem cell transplantation (HSCT). Gemtuzumab ozogamicin (GO, anti‐CD33 linked to calicheamicin) was recently approved to treat frontline AML patients in combination with daunorubicin and cytarabine. GO has also shown some activity in relapse AML, particularly in the core binding factor (CBF) subgroup (Hospital MA, Blood 2014). Whether the use of standard anthracyclines is required when combined to anthracycline‐like calicheamicin remains to be explored.Aims:To assess the efficacy and safety of GO combined with cytarabine (GO+AraC) to treat AML patients in first relapse.Methods:We conducted a retrospective monocentric study of relapsed AML patients in Saint‐Louis Hospital (Paris, France). Between Jan 2008 and Dec 2018, all consecutive patients with AML in first relapse treated with GO (3 mg/sqm/d for 3 days or 6 mg/sqm for 1 day) plus AraC (1–3 g/sqm/bid for 3–5 days or 200 mg/sqm/d for 7 days in continuous infusion) were included. GO was provided through the French compassionate use program (ATU). Patients and disease characteristics, safety, and outcome are reported.Results:A total of 71 patients with a median age of 46 years old (range, 17–77) were included. ELN‐2010 classification was favorable in 42 patients (59%, including 31 CBF‐AML), intermediate in 19 patients (27%), and unfavorable in 10 patients (14%). Median percentage of CD33 expression on blast cells was 87% (range, 22–100). Five patients (7%) had been transplanted in first CR. Median time to relapse was 10 months (range, 5–140). Median follow up was 1.5 years (range, 0.1–10.1). Overall Response Rate (ORR) after salvage was 77% (N = 55) with 52 patients (74%) achieving CR. Time to relapse >12 months (p = .04) and CD33 expression >70% (p = .05) (Olombel G., Blood 2016) were the only factors significantly associated with increased ORR. Among patients with OR, 18 (33%) were consolidated with HDAC alone (38%) and 26 with HDAC+GO (55%). Thirty‐two patients (58%) were bridged to HSCT in CR2. During salvage, a grade 3/4 hepatic toxicity was found in 16 patients (22%) including 6 sinusoidal obstruction syndromes (SOS). A total of 11 patients (15%) experienced SOS with 1/5 patients with previous HSCT and 4/32 after subsequent HSCT (13%). Non‐relapse mortality at 3 years was 12% (95%CI, 6–23) with 2 SOS, 2 sepsis, and 2 hemorrhage. The 3‐year cumulative Incidence of relapse (CIR) was 55% (95%CI, 40–71). In univariate and multivariate analyses, factors significantly associated with increased CIR were a short time to relapse (<12 months), unfavorable ELN classification, and the use of continuous AraC during induction. The 3‐year overall survival (OS) was 43% (95%CI, 30–56). Factors associated with decreased OS were a shorter time to relapse and unfavorable ELN status (Figure). In patients bridged to HSCT, 3‐year OS was 61% (95%CI, 40–77), with no difference between ELN favorable and intermediate subgroups.Summary/Conclusion:In patients with AML in first relapse, GO+Arac is a safe and efficient salvage regimen, especially in patients with ELN favorable/intermediate profile and time to relapse of more than 12 months.image