July, 2024

No. 109 (7)

2023 CiteScore: 14.1 2023 Impact Factor: 8.2



Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors

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.

Yuqin Song et al.


Selection of dormant cells during treatment of T-lineage lymphoblastic leukemia and CREB as a therapeutic target

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.

Dino Masic et al.


Characterization of zanubrutinib safety and tolerability profile and comparison with ibrutinib safety profile in patients with B-cell malignancies: post-hoc analysis of a large clinical trial safety database

Zanubrutinib is a next-generation Bruton tyrosine kinase (BTK) inhibitor designed to minimize off-target toxicities seen during treatment with ibrutinib. Brown and colleagues present results of a pooled safety analysis of zanubrutinib monotherapy using data from ten different studies, involving more than 1,500 patients with B-cell malignancies treated with zanubrutinib. Zanubrutinib remained well tolerated, with no emergence of new safety signals, even at a median treatment duration of approximately 3 years.

Jennifer R. Brown et al.


GPIbα CAAR T cells function like a Trojan horse to eliminate autoreactive B cells to treat immune thrombocytopenia

RNovel therapeutic strategies for refractory immune thrombocytopenia (ITP), are needed. Glycoprotein (GP) Ibα is a significant autoantigen found in ITP patients and is associated with poor response to standard immunosuppressive treatments. Zhou and colleagues chose GPIbα to engineer human T cells to express a chimeric autoantibody receptor (CAAR) with GPIbα constructed into the ligand-binding domain fused to the CD8 transmembrane domain and CD3ζ-4-1BB signaling domains. They tested, through in vitro and in vivo experiments, the GPIbα CAAR T cells and presented a proof of concept that CAAR T-cell therapy could eradicate autoimmune B cells while sparing healthy B cells.

Jie Zhou et al.