Venetoclax Resistance Emerges as Challenge in CLL Therapy, SPHK2 Inhibition Shows Promise

Resistance to venetoclax, a $2.5 billion CLL therapy, is emerging as a challenge, with leukemic cells persisting despite combination therapy. Sphingosine kinase 2 (SPHK2) is overexpressed in resistant cells, and its inhibition may reduce T-cell-induced activation and proliferation of resistant CLL cells. A new in vivo study shows that adding opaganib, a potent SPHK2 inhibitor, to venetoclax reduces CLL cell counts by 50% and lowers T cell counts and PD1 expression. This suggests potential for opaganib as a therapeutic add-on in CLL.