Chlorambucil

Approved in 1957, chlorambucil is indicated for chronic lymphocytic leukaemia and malignant lymphomas including lymphosarcoma, giant follicular lymphoma and Hodgkin disease; the label states it is palliative rather than curative. It was the comparator arm in the trials that established fludarabine, alemtuzumab and, with obinutuzumab (CLL11), the chemoimmunotherapy era in unfit CLL patients, and it is still used with an anti-CD20 antibody in frail patients where BTK inhibitors or venetoclax are unavailable. Myelosuppression is dose-limiting; long-term use increases the risk of secondary leukaemia and it is teratogenic and impairs fertility.