Imbruvica (ibrutinib)

P1, N=39, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2027

Importantly, these changes correlated with favorable response to ibrutinib, where chromatin accessibilities of TCF7 (encoding TCF1) and BCL11B were increased and TCF1 interacted with BCL11B to restore T cell immunity, but not in patients with poor response to ibrutinib. These findings suggest that the emergence and increase of BCL11B + TCF1 + CD8+ Teff cells likely reflect reconstitution of T cell immunity induced by ibrutinib.

Covalent BTKi (cBTKi) such as ibrutinib, acalabrutinib, and zanubrutinib are effective but alterations in the kinase domain at C481 or BTK gatekeeper residue T474 mutations result in development of resistance...We evaluated the efficacy of a new ncBTKi, docirbrutinib (AS-1763), against 14 BTK mutants, including C481S, T474x, and L528x, as well as gatekeeper and kinase domain double mutants, using biochemical assays, cell-line models, and primary CLL lymphocytes. Docirbrutinib potently inhibited BTK autophosphorylation and mutant BTK-driven cell proliferation, with greater effects than ibrutinib and pirtobrutinib against certain mutants. In treatment-naïve and relapsed/refractory CLL samples, docirbrutinib disrupted B-cell receptor signaling and sensitized cells to apoptosis induced by venetoclax and AZD5991. In a dose-escalation trial (NCT05602363), docirbrutinib decreased CCL3/CCL4 biomarkers and inhibited the B-cell receptor pathway signaling in longitudinal samples from patients with relapsed/refractory CLL. These findings establish docirbrutinib as a pan-mutant ncBTKi with potential to improve outcomes for CLL patients, including those with disease resistant to cBTKi and other ncBTKi.

In younger, fit patients, first-line therapy traditionally involves dose-intensified chemoimmunotherapy with high-dose cytarabine and autologous stem-cell transplantation (ASCT). The incorporation of Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, into induction regimens has improved survival outcomes, with emerging evidence that may limit the use of ASCT to high-risk subsets...In older or transplant-ineligible patients, bendamustine-rituximab remains a backbone therapy, with chemotherapy-free combinations incorporating BTKi, BCL2 inhibitors, and anti-CD20 antibodies offering effective, well-tolerated alternatives...Ongoing trials are evaluating optimal sequencing and combination strategies to improve outcomes, particularly in high-risk and cBTKi-exposed patients. Overall, modern MCL management emphasizes individualized therapy based on biological risk, functional status, and treatment tolerability, with novel targeted and cellular approaches reshaping the frontline and relapsed treatment landscape.

Chemotherapeutics exacerbate cardiovascular risk: anthracyclines (e.g., doxorubicin) boost ICaL and RyR2 leak; platinums delay INa decay; TKIs (e.g., ibrutinib) broadly suppress currents kinase-dependently. Integrating in vitro/experimental molecular data, this review maps class-specific electrophysiological impacts in the heart, highlighting safety pharmacology's role in risk mitigation and informing therapeutic, regulatory, and public health strategies to safeguard cardiovascular resilience against pervasive chemical threats.

P2, N=41, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P2, N=18, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P1, N=120, Enrolling by invitation, Janssen Research & Development, LLC | N=52 --> 120

The poor prognosis of TP53-mutant DLBCL is dependent on intrinsic features, such as VAF, and modulated by co-occurring genomic lesions or lymphoma cell-intrinsic or microenvironmental expression patterns.

These findings demonstrate that Wenxin Granules can ameliorate the occurrence and progression of AF induced by ibrutinib treatment, thereby laying the groundwork for further research and potential clinical applications in AF therapy.

OxPhos inhibitor IACS-010759 demonstrated synergy with AZD4573 in vitro. Thus, CDK9 inhibition exhibits activity in ibrutinib-resistant MCL and can be further enhanced by co-targeting of OxPhos.

Development of the first-generation BTK inhibitor (BTKi), ibrutinib, revolutionized the treatment of B-cell malignancies. Based on limited available data, BTK does not seem to have a prominent role in the pathogenesis of AD, and its role in asthma is unclear, thus necessitating further clinical research. Remibrutinib and rilzabrutinib have shown the most promise in allergic and autoimmune diseases to date; remibrutinib is approved in adults with CSU, and rilzabrutinib is approved in adults with persistent or chronic immune thrombocytopenia.