Umbralisib was found to be well tolerated and led to clinical benefit in heavily pretreated patients with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL), according to the results of a study published in the Journal of Clinical Oncology.

The multicohort, open-label, phase 2b UNITY-NHL study ( Identifier: NCT02793583) included 208 patients with R/R marginal zone lymphoma (MZL), follicular lymphoma (FL), or small lymphocytic lymphoma (SLL) who were unresponsive to previous treatment, including at least 1 anti-CD20-based therapy. Patients received umbralisib, a dual inhibitor of PI3Kδ/casein kinase-1ε, 800 mg orally once daily until disease progression, unacceptable toxicity, or study withdrawal.

Overall response rate (ORR), which was defined as the percentage of patients who achieved a complete response (CR) or partial response (PR), was the primary endpoint.

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Participants were enrolled from May 2017 through September 2018: 69 patients had MZL, 117 patients had FL, and 22 had SLL. The intent-to-treat (ITT) cutoff date was July 13, 2020. The median age of the cohort was 66 years (range, 29-88), 56.7% were men, and 81.7% were White.

After a median follow-up of 27.7 months, the ORR was 47.1% for the ITT population, as assessed by an independent review committee. ORRs for patients with MZL, FL, and SLL, respectively, were 49.3% (95% CI, 37.0-61.6), 45.3% (95% CI, 36.1-54.8), and 50.0% (95% CI, 28.2-71.8).

The median duration of response was not reached in patients with MZL (95% CI, 10.3 to not estimable [NE]) and was 11.1 months (95% CI, 8.3-15.6) for patients with FL and 18.3 months (95% CI, 2.4 to NE) for patients with SLL. The median time to response (95% CI) for patients with MZL, FL, and SLL, respectively, was 2.8 months (2.7-2.9), 4.6 months (3.0-5.6), and 2.7 months (2.4-2.8).

The median progression-free survival was not reached in patients with MZL (95% CI, 12.1 to NE) and was 10.6 months (95% CI, 7.2-13.7) for those with FL and 20.9 months (95% CI, 7.4-24.1) for those with SLL.

A total of 207 patients (99.5%) experienced a treatment-emergent adverse event (TEAE); 53.4% had 1 or more grade ≥3 events. Diarrhea (59.1%), nausea (39.4%), fatigue (30.8%), vomiting (23.6%), and cough (20.7%) were the most commonly reported TEAEs.

TEAEs led to discontinuation of umbralisib in 32 patients (15.4%). The 2 grade ≥3 adverse events (AEs) that occurred in at least 10% of patients were neutropenia (11.5%) and diarrhea (10.1%; all grade 3). Serious TEAEs were reported by 63 patients (30.3%), with grade ≥3 serious TEAEs occurring in 54 patients (26.0%). A total of 36 patients (17.3%) reported serious TEAEs that were considered related to umbralisib.

“In UNITY-NHL, umbralisib showed meaningful clinical activity in patients with R/R iNHL consistent with that demonstrated by prior inhibitors of PI3K,” the study authors commented. “However, the safety profile appears improved compared with first-generation PI3K inhibitors, with manageable toxicities and a relatively low number of AE-related discontinuations.”

Disclosure: UNITY-NHL was designed and sponsored by TG Therapeutics. Some of the study authors reported affiliations with biotechnology, biopharmaceutical, and pharmaceutical companies, including TG Therapeutics. Please see the original reference for a full list of authors’ disclosures.


Fowler NH, Samaniego F, Jurczak W, et al. Umbralisib, a dual PI3Kδ/CK1ε inhibitor in patients with relapsed or refractory indolent lymphoma. J Clin Oncol. Published online March 8, 2021. doi:10.1200/JCO.20.03433