idelalisib + chlorambucil

**Idelalisib + chlorambucil** is a combination regimen under investigation for the treatment of chronic lymphocytic leukemia (CLL), particularly in patients with relapsed/refractory disease and high-risk features. - **Idelalisib** is a highly selective oral inhibitor of the delta isoform of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3Kδ), primarily expressed in leukocytes. By inhibiting PI3Kδ, idelalisib disrupts B cell receptor signaling, induces apoptosis in malignant B cells, and impairs their migration and survival through multiple downstream effects (e.g., inhibition of AKT, MAPK signaling, and chemokine/cytokine responses)[1][3][7]. - **Chlorambucil** is a DNA-alkylating antineoplastic agent that cross-links DNA, disrupts replication and transcription, and leads to apoptosis via several mechanisms (fragmentation, cross-link formation, mispairing)[2][6]. - The combination aims to integrate targeted PI3Kδ inhibition with classical DNA-damaging chemotherapy, enhancing efficacy in overcoming resistance seen in high-risk CLL populations. Clinical data (multi-arm phase Ib trial) have shown notable activity, with overall response rates around 67% and manageable, though significant, hematologic toxicity (e.g., neutropenia, thrombocytopenia, anemia, diarrhea, transaminitis)[1][7].

Other names

idelalisib and chlorambucil