Scientific Reports (Jun 2022)

Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML

  • Emmanuel Gyan,
  • Arnaud Pigneux,
  • Mathilde Hunault,
  • Pierre Peterlin,
  • Martin Carré,
  • Jacques-Olivier Bay,
  • Caroline Bonmati,
  • Maria-Pilar Gallego-Hernanz,
  • Bruno Lioure,
  • Philippe Bertrand,
  • Nicolas Vallet,
  • David Ternant,
  • François Darrouzain,
  • Frédéric Picou,
  • Marie-Christine Béné,
  • Christian Récher,
  • Olivier Hérault

DOI
https://doi.org/10.1038/s41598-022-13626-y
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 9

Abstract

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Abstract The treatment of acute myeloid leukemia (AML) with unfavorable cytogenetics treatment remains a 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. The FILO group launched a pilot clinical study to evaluate the feasibility, safety, and efficacy of the adjunction of a commercial FO emulsion to 3 + 7 in untreated AML with unfavorable cytogenetics. The primary objective was complete response (CR). Thirty patients were included. FO administration raised the plasma levels of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids (p < 0.001). The pharmacokinetics of cytarabine and daunorubicin were unaffected. A historical comparison to the LAM2001 trial (Lioure et al. Blood 2012) found a higher frequency of grade 3 serious adverse events, with no drug-related unexpected toxicity. The CR rate was 77%, and the partial response (PR) 10%, not significantly superior to that of the previous study (CR 72%, PR 1%). RT-qPCR analysis of Nrf2 target genes and antioxidant enzymes did not show a significant in vivo response. Overall, FO emulsion adjunction to 3 + 7 is feasible. An improvement in CR was not shown in this cohort of high-risk patients. The present data does not support the use of FO in adjunction with 3 + 7 in high-risk AML patients. ClinicalTrials.gov identifier: NCT01999413.