Sovleplenib is a selective spleen tyrosine kinase (Syk) inhibitor with anti-tumor activity in preclinical models of B-cell malignancy. Targeting Syk signaling, which is upstream of both Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3Kδ), may overcome drug resistance to BTK inhibitors or PI3Kδ inhibitors. Song and colleagues present results of a phase I trial to determine the safety, tolerability, efficacy and pharmacokinetics of sovleplenib in patients with relapsed/refractory mature B-cell malignancies in China.

The slower clearance of acute lymphoblastic leukemia (ALL) cells during therapy is one of the ways through which multidrug resistance reveals itself. In their study on T-cell ALL Masic and colleagues, through the use of single-cell, high dimensional mass cytometry, show the presence of the activated cAMP response element-binding (CREB) pathway in almost all viable cell clusters during therapy, and, moreover, they demonstrate the sensitivity of the leukemic cells to CREB inhibition and that minimal residual disease (MRD) is made up of non-cycling cells selected during therapy. These results suggest that MRD-directed therapies should be cell-cycle independent and that the CREB pathway is a valid therapeutic target for T-cell ALL.