Idelalisib for relapsed/refractory indolent B-cell non-Hodgkin's lymphoma: an overview of pharmacokinetics and clinical trial outcomes.
Indolent non-Hodgkin's lymphoma (iNHL) describes a group of B-cell lymphomas with a long median survival and a relapsing-remitting clinical course. Although existing treatments are initially effective, patients often relapse, demonstrating decreasing efficacy with successive treatment courses. Alternative treatments are needed. PI3Kδ plays an essential, non-redundant role in B-cell receptor signaling critical to the pathogenesis of iNHL. It is expressed predominantly in hematopoietic cells, making PI3Kδ an attractive therapeutic target. Idelalisib is an oral PI3Kδ inhibitor approved in 2014 in the USA and the EU as monotherapy in relapsed follicular lymphoma or relapsed small lymphocytic lymphoma previously treated with two or more prior systemic therapies, or as part of combination therapy with rituximab in patients with chronic lymphocytic leukemia, for whom rituximab monotherapy would be considered appropriate due to the presence of comorbidities. Herein, we review the available data for idelalisib, with an emphasis on relapsed/refractory B-cell iNHL.
a Cancer Sciences Division, Somers Cancer Research Building, Southampton General Hospital, Mailpoint 824, Southampton, S016 6YD, UK.
Andrew
A
Davies
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; C552946:idelalisib
CAL-101; GS-1101; PI3K; clinical; idelalisib; non-Hodgkin’s lymphoma; pharmacokinetics; refractory; relapsed; rituximab