Duvelisib: a new phosphoinositide-3-kinase inhibitor in chronic lymphocytic leukemia

P110-gamma and -delta act in lymphocytes chemotaxis, presenting distinct, nonredundant roles in B- and T-cell migration and adhesion to stromal cells. Moreover, phosphoinositide-3-kinase-gamma inhibition contributes to regulate macrophage polarization inhibiting cancer growth. Duvelisib (IPI-145) is an oral first-in-class, dual phosphoinositide-3-kinase inhibitor targeting p110-delta/gamma exerting its activity in preclinical studies across different prognostic groups. In a large Phase III study, duvelisib showed superior progression-free survival and overall response rate compared with ofatumumab, thus leading to its approval for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Immune-related effects are the main reason for treatment suspension, thus affecting survival benefit. Nevertheless, the correct management of adverse events, eventually including dose modification, allows patients to remain on treatment. In conclusion, duvelisib represents a promising treatment in chronic lymphocytic leukemia and a salvage therapy after ibrutinib.