Leuk Res: Docepastat (DSTAT), a CXCL12/CXCR4 inhibitor, in combination with azacitidine for the treatment of hypomethylating agent-refractory AML and MDS

Leukemia stem cells utilize cell adhesion molecules, such as CXCR4/CXCL12, to home to the bone marrow stromal microenvironment, where they remain in a dormant, protected state
.

Docetaxel sodium (DSTAT, CX-01) is a low anticoagulant heparin with multiple mechanisms of action including inhibition of the CXCR4/CXCL12 axis, blockade of HMGB1 and binding to platelet factor 4 (PF-4)

Leukemia stem cells utilize cell adhesion molecules, such as CXCR4/CXCL12, to home to the bone marrow stromal microenvironment, where they remain in a dormant, protected state

A research team conducted a pilot study of adding DSTAT to azacitidine in patients with AML or MDS who had not responded to or had relapsed to prior hypomethylating drug therapy, hypothesizing that DSTAT might improve response rates

Table 1: Characteristics of patients and diseases
.

Table 1: Characteristics of patients and diseases
.

Table 2: Grade III/IV adverse events that occurred during treatment with DSTAT and azetidine
.

Table 2: Grade III/IV adverse events that occurred during treatment with DSTAT and azetidine
.

Of the 15 patients with evaluable response, 1 had a complete response and 3 had a bone marrow response, resulting in a response rate of 27% of evaluable patients (20% overall)
.

Hematological improvement was observed in 5 additional patients

Of the 15 patients with evaluable response, 1 had a complete response and 3 had a bone marrow response, resulting in a response rate of 27% of evaluable patients (20% overall)

Figure 1: Overall survival of all patients treated with DSTAT and azacytidine
.

Figure 1: Overall survival of all patients treated with DSTAT and azacytidine
.

Figure 2: Fluorescence-activated cell sorting on day 1 1 (C1D1), C1D3, C1D7, and C2D1, comparing responders and non-responders (n=11), found a slight increase in absolute numbers of circulating NKT cells in C1D3 and C2D1 (* means p<0.
05)
.

No significant differences in myeloblast mobilization or other immune cell subsets were observed at these time points during treatment with DSTAT and azacytidine

Figure 2: Fluorescence-activated cell sorting on day 1 1 (C1D1), C1D3, C1D7, and C2D1, comparing responders and non-responders (n=11), found a slight increase in absolute numbers of circulating NKT cells in C1D3 and C2D1 (* means p<0.

In conclusion, this trial demonstrated the feasibility of combining DSTAT with azacitidine, and several responses were observed, suggesting that this combination deserves further study

Original source:

Huselton E, Rettig MP, Campbell K, Cashen AF, DiPersio JF, Gao F, Jacoby MA, Pusic I, Romee R, Schroeder MA, Uy GL, Marcus S, Westervelt P.

Huselton E, Rettig MP, Campbell K, Cashen AF, DiPersio JF, Gao F, Jacoby MA, Pusic I, Romee R, Schroeder MA, Uy GL, Marcus S, Westervelt P.
Combination of dociparstat sodium (DSTAT), a CXCL12/ CXCR4 inhibitor, with azacitidine for the treatment of hypomethylating agent refractory AML and MDS.
Leuk Res.
2021 Nov;110:106713.
doi: 10.
1016/j.
leukres.
2021.
106713.
Epub 2021 Sep 22.
PMID: 34619434.
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