BI 836826 + ibrutinib

**BI 836826 + ibrutinib** is a combination therapy studied for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). BI 836826 is a chimeric mouse–human monoclonal antibody that targets CD37, a transmembrane protein present on normal and malignant B cells, and is engineered to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) against CLL cells. Ibrutinib is a small molecule inhibitor of Bruton tyrosine kinase (BTK), which is critical for B-cell receptor signaling in malignant B cells. The rationale for combining these agents lies in their complementary mechanisms: ibrutinib inhibits BTK-mediated survival and proliferation of CLL cells, while BI 836826 provides direct immune-mediated cytotoxicity. The combination was investigated in a phase Ib, open-label, dose-escalation study in patients with relapsed/refractory CLL, demonstrating an acceptable safety profile at the studied doses, with promising response rates, though clinical development was discontinued before reaching maximum tolerated dose or recommended phase II dose.