CTI BioPharma Presents Data Showing Treatment With Pacritinib

(RTTNews) - CTI BioPharma Corp. (CTIC) announced results showing treatment with pacritinib, an investigational oral multikinase inhibitor in Phase 3 clinical development, preferentially killed acute myeloid leukemia or AML cells with FLT3 mutations, overcame stromal protection and suppressed leukemic outgrowth from stroma adherent AML cells in both medium-term and long-term assays.

According to the company, the efficacy of pacritinib was assessed in 62 primary AML samples that either carried a mutation in FLT3 or had wild type FLT3. A MS5 stromal co-culture model was used to assess FLT3-ITD cells that are adherent to non-adherent to stroma. The results showed that FLT3-ITD cells were more sensitive to pacritinib treatment compared to wild type samples and retained sensitivity to pacritnib treatment after seven days of co-culture with MS5 stroma cells.

Following seven days of treatment, stroma-adherent FLT3-ITD cells had sustained suppression of leukemic outgrowth at 14 days. To assess long-term suppression of growth, the CD34+38- FLT3-ITD subpopulation of cells, which have in vivo engrafting ability, a leukemic stem cell property, and correlate with risk of clinical relapse, were plated with MS5 stroma cells. Pacritinib treatment significantly reduced cobblestone area forming cell or CAFC frequency at five weeks.

The company said that Leukemic cell signaling was measured by culturing FLT3-ITD cells on stroma in the presence of pacritinib for up to 24 hours. Activity of the p-STAT5, JAK2, AKT and ERK signaling pathways was assessed by immunoblot and luminescent assays.

The authors concluded that pacritinib has the potential to overcome environmentally mediated drug resistance in FLT3 positive AML and demonstrated good synergy with cytarabine and a MEK inhibitor.