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J. Pidala et al.
P=0.68
P=0.014
Figure 5. Serum concentration of ST2 and REG3α at day 7 post-HCT.
trointestinal tract (GI). REG3α was significantly reduced in the ustekinumab-treated subjects at day 7 post HCT, suggesting that neutralization of IL-12/IL-23p40 may ame- liorate early damage to the GI tract that ultimately cas- cades into GvHD lethality. This finding also requires con- firmation in a subsequent trial. While there are conflicting data regarding the relative contribution of Th2 (vs. other Th subsets) to chronic GvHD development, our study demonstrates no evidence of worsened chronic GvHD after IL-12/IL-23p40 neutralization.
We acknowledge as a limitation that IL-12/IL-23p40 neutralization together with sirolimus/tacrolimus did not offer patients complete protection from acute GvHD. Additional dosing of ustekinumab beyond the studied
approach may offer benefit, as anti-IL-12/IL-23p40 anti- body levels declined and IL-12/IL-23p40 cytokine levels increased in the range of 50-60 days post HCT onward. Future trials could incorporate prolonged maintenance dosing modeled after approved maintenance therapy in psoriasis and Crohn disease.
Funding
We acknowledge the following funding support: Gateway for Cancer Research (to JP) G12-900 (inclusive of trial costs and study drug costs), American Cancer Society MRSG-11-149-01- LIB, Moffitt Cancer Center Support Grant P30 CA076292 (flow cytometry, analytical pharmacology, biostatistics, and ana- lytic microscopy cores).
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