Why PI3K Is a Target and What Makes Duvelisib Different

Brammer and Zinzani examine the rationale for targeting phosphoinositide 3-kinase in T-cell lymphoma and explain why duvelisib has shown activity where other agents in the class have disappointed. Zinzani recalls early single-agent experience reported more than a decade ago, when duvelisib produced notably high response rates in peripheral and cutaneous T-cell lymphoma before development was redirected toward B-cell indications. He highlights duvelisib as distinctive among PI3K inhibitors for its activity in peripheral T-cell disease. The discussion turns to disease biology, including the reclassification of angioimmunoblastic T-cell lymphoma within the broader T-follicular helper group and the recognition that this category, together with peripheral T-cell lymphoma not otherwise specified and anaplastic large-cell lymphoma, accounts for the large majority of cases. Both experts frame T-follicular helper disease as biologically ripe for targeting, which directly shaped the design of the PRIMO study and its emphasis on efficacy across histologic subtypes.