Professor Régis Peffault de Latour, coordinator of the MaRIH network, presented at ASH the results of a prospective international phase II study—the first-in-human evaluation of a humanized antibody targeting the gamma subunit of the IL-2 receptor in severe aplastic anemia.

This subunit is part of the complex forming the receptor for interleukins dependent on the common gamma chain.

The antibody therefore blocks the JAK/STAT signaling pathway, affecting the development and homeostasis of T and NK lymphocytes. It had previously shown promising results in mice, in an experimental primate model, and in a murine model of GvHD with immune-mediated bone marrow failure.

The primary endpoint of tolerability was met, with no serious complications related to the experimental treatment. All complications observed were associated with the underlying aplastic anemia.

Concomitant assays showed an increase in gamma-dependent cytokines (likely due to increased production and lack of consumption resulting from antibody-mediated blockade), as well as a decrease in inflammatory molecules (IFN-γ) and effector molecules (Granzyme B).

After a transient increase, CD4 and CD8 T lymphocytes, as well as NK cells, were reduced.

In terms of efficacy, only one patient out of the 17 included responded. She relapsed six months later and responded again to a second antibody injection. It should be noted that the patient population had very severe aplastic anemia, with some patients having received up to six prior lines of treatment, which explains the low response rate.

These results suggest the potential for using this antibody at an earlier stage of aplastic anemia treatment, and possibly in other immune-mediated diseases such as graft-versus-host disease.