Adjunction of a Fish Oil Emulsion to Cytarabine and Daunorubicin Induction Chemotherapy in High-Risk AML. the Famyly Pilot Study from the French Innovative Leukemia Organization (FILO)

Background. Acute myeloid leukemia (AML) with unfavorable cytogenetics remains a therapeutic challenge. We previously established that ex vivo exposure of AML blasts to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or fish oil emulsion (FO) induces Nrf2 pathway activation, metabolic switch and cell death (Picou et al., Pharmacol Res 2018;136:45-55). Objectives. The FILO group launched a pilot clinical study to evaluate the feasibility, safety and efficacy of the adjunction of a commercial FO emulsion (OMEGAVEN) to 3+7 in untreated AML with unfavorable cytogenetics. Patients and methods. The FAMYLY trial was a multicenter single-arm phase II study. Eligible patients had a diagnosis of untreated AML with unfavorable cytogenetics, 18 years old or above. For patients with WBC = 30 G/L, FO and 3+7 were started concomitantly, and FO was administered until day 9. The primary objective was complete response (CR) on the BM aspirate at the end of induction. Data from 75 patients with adverse cytogenetics and treated with daunorubicin and cytarabine in LAM2001 study (Lioure et al., Blood 2012) was used as a historical control. Serial blood samples were collected before treatment, and on days 1 and 3 after start of treatment, to evaluate the expression of NRF-2 target genes and antioxidant enzymes by RT-qPCR. Results. Thirty patients were included. The median age was 54 years (range: 30-64 years), and only 3 patients were hyperleukocytic. FO administration raised the plasma levels of EPA and DHA (p Conclusions. Altogether, FO emulsion adjunction to 3+7 is feasible and safe. Although CR rate improvement was not shown in this cohort of high-risk patients, further research aiming at finding the sufficient dose to trigger an NRF-2 response in vivo should be considered. ClinicalTrials.gov identifier: NCT01999413. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: OMEGAVEN (fish oil emulsion) in Acute Myeloid Leukemia