Imbruvica (ibrutinib)

P2, N=9, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=20 --> 9

P3, N=737, Recruiting, Loxo Oncology, Inc. | Trial primary completion date: Jun 2025 --> Oct 2027

Second, a network meta-analysis ranked the efficacy and safety of regimens including rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R); R-CHOP plus lenalidomide (R2-CHOP); R-CHOP plus ibrutinib (I+R-CHOP); R-CHOP plus zanubrutinib (Z+R-CHOP); and R-CHOP plus venetoclax (Ven-R-CHOP). DEL is a distinct high-risk subtype with quantifiable prognostic detriment. Z+R-CHOP emerges as a promising strategy requiring validation in prospective studies.

POLA demonstrated robust single-agent antitumor activity in vivo, including in PDX models derived from patients with ibrutinib-resistant MCL. This signature likely reflects core pathways associated with POLA resistance and highlights potential novel therapeutic vulnerabilities. These findings strongly support further clinical investigation of POLA in combination with VEN as a BCL2- and MCL1-targeting therapeutic strategy in patients with R/R MCL and BCL2-positive R/R DLBCL.

P3, N=700, Recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2027 --> Dec 2029

P1/2, N=38, Recruiting, Yazeed Sawalha | Trial completion date: Dec 2028 --> Oct 2027 | Trial primary completion date: Dec 2026 --> Aug 2027

P1/2, N=217, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2027 --> May 2028

Bruton tyrosine kinase inhibidors (BTKI), such as ibrutinib and zanubrutinib, represent a cornerstone of CLL/SLL treatment by inhibiting B-cell receptor signaling. The patient improved after BTKI reintroduction, and a P-RT was diagnosed. Nine similar patients were found through PubMed search, and we describe their clinicopathological characteristics.

P1, N=34, Active, not recruiting, National Cancer Institute (NCI) | N=55 --> 34 | Recruiting --> Active, not recruiting

P1/2, N=85, Active, not recruiting, Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting | Not yet recruiting --> Active, not recruiting

Here, we investigated non-genetic mechanisms of ibrutinib resistance in marginal zone lymphoma (MZL) and their broader therapeutic implications. Pharmacological or genetic disruption of the IL-16/CD9/PI3K axis restored sensitivity to BTK inhibitors and R-CHOP and abrogated IL-16-induced signaling in primary CLL samples. In conclusion, an IL-16/CD9-driven, epigenetically regulated survival pathway represents one possible mechanism of resistance to BTK inhibitors and chemoimmunotherapy, supporting therapeutic targeting of this axis in refractory B-cell lymphomas.

Furthermore, both the CD79B/BTK inhibitor Ibrutinib and the STAT3 agonist GCDA potentiated the cytotoxicity of the clinical MM drug Ixazomib. In summary, our findings establish that the APN inhibitor Bestatin induces MM cell differentiation via the CD79B/BTK-STAT3 signaling axis. Targeting this pathway represents a promising strategy to enhance the efficacy of Ixazomib, providing a compelling rationale for novel combination therapies in MM.