CAL-101: a phosphatidylinositol-3-kinase p110-delta inhibitor for the treatment of lymphoid malignancies

Introduction: The management of lymphoid malignancies has greatly evolved in the last decade with the advent of targeted therapies, which have improved response and survival in patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and plasma cell myeloma (PCM). The PI3K pathway seems to play a seminal role in the development of lymphoid malignancies. CAL-101 is a highly selective PI3K p110 delta inhibitor currently undergoing clinical development. Areas covered: The aims of this review are to summarize our understanding of the PI3K pathway, its role in lymphoid malignancies, the preclinical and clinical experience accumulated with CAL-101, a PI3K delta inhibitor, and potential areas of future development. Expert opinion: CAL-101 is a novel drug that has shown preclinical activity against CLL, NHL, HL and PCM cells. There is early evidence of clinical efficacy in CLL and indolent NHL. Studies using CAL-101 alone or in combination are also ongoing in PCM, HL and aggressive NHL. However, additional studies are needed to prove CAL-101 is effective and safe as the goals of therapy for patients with lymphoid neoplasms are not only directed towards improving response and cure rates but also prolonging survival without affecting quality of life.