Immunotherapy with histamine dihydrochloride for the prevention of relapse in acute myeloid leukemia

Abstract

Most patients with acute myeloid leukemia (AML) achieve complete remission (CR) after induction chemotherapy. Despite ensuing courses of consolidation chemotherapy, a large fraction of patients will experience relapses with poor prospects of long-term survival. Histamine dihydrochloride (HDC) in combination with the T-cell-derived cytokine IL-2 was recently approved within the EU as a remission maintenance immunotherapy in AML. HDC reduces myeloid cell-derived suppression of anti-leukemic lymphocytes, and aims to unravel a therapeutic benefit of IL-2 in AML by improving natural killer and T-cell activation. A randomized Phase III trial with 320 AML patients in CR demonstrated a significant reduction of relapse risk after immunotherapy with HDC plus low-dose IL-2 in the post-consolidation phase. HDC is the first approved therapeutic to target the state of immunosuppression in AML; further development in this area may comprise supplementary or alternative counter-suppressive agents with the aim to improve the efficacy of cancer immunotherapy.

Keywords::

• acute myeloid leukemia
• cytotoxic T lymphocyte
• histamine dihydrochloride
• IL-2
• immunotherapy
• NADPH oxidase
• natural killer cell

Financial & competing interests disclosure

Kristoffer Hellstrand holds patents related to the work described in this study. Kristoffer Hellstrand and Mats Brune are consultants to the EpiCept Corporation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.