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Rationale for Treating Marginal Zone Lymphoma With PI3K-Delta Inhibitor Umbralisib

Lori A. Leslie, MD
Published Online:3:51 PM, Tue July 9, 2019


Lori A. Leslie, MD, a lymphoma attending at John Theurer Cancer Center, discusses the rationale for investigating the PI3K-delta inhibitor umbralisib (TGR-1202) in patients with relapsed or refractory marginal zone lymphoma (MZL) in a multi-center, open-label phase II study. On trial, only patients with MZL were enrolled who had received at least 1 prior line of therapy. These patients received single-agent umbralisib once daily until progression or unacceptable toxicity.

Based on findings reported at the 2019 American Association for Cancer Research (AACR) Annual Meeting, an objective response rate (ORR) of 52% was demonstrated in this patient population. In addition, Leslie says that 19% of patients achieved a complete response (CR).

Updated results presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting showed that the ORR was 57% in patients with extranodal MZL, 42% in patients with nodal MZL, and 43% for patients with splenic MZL. Additionally, the ORR was 52% in patients who had received at least 2 prior lines of therapy. 

Although other PI3K inhibitors can induce stable disease and partial responses in MZL, 19% of patients achieving a CR is higher than what’s been noted historically for this group of agents, Leslie notes.

Umbralisib is a newer-generation PI3K-delta inhibitor. Leslie says that umbralisib inhibits the PI3K-delta isoform, enhances specificity for the delta isoform, and has somewhat of an effect on T-regulatory cell function and numbers. In addition, umbralisib has demonstrated lower safety signals in terms of immune toxicities compared with other PI3K inhibitors, says Leslie.
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