Umbralisib Confers Durable Response, Tumor Reductions in Patients With Relapsed/Refractory Marginal Zone Lymphoma

While rituximab-based treatment has improved outcomes for patients with marginal zone lymphoma (MZL), most patients eventually have a disease relapse. According to results from an ongoing study presented at the 2019 American Association for Cancer Research Annual Meeting, umbralisib monotherapy led to responses in more than half of patients with relapsed/refractory MZL. The responses also appeared to be durable, reported lead author Nathan H. Fowler, MD, of the MD Anderson Cancer Center in Houston.

“Umbralisib is a small-molecule inhibitor that targets PI3K-delta, which is a component of a signaling pathway that has a key role in promoting the survival and expansion of many types of cells,” said Dr. Fowler. “[Our findings] suggest that this oral targeted therapeutic has significant activity against relapsed/refractory MZL and offers hope for patients.”

Eligible participants had histologically confirmed MZL, an Eastern Cooperative Oncology Group performance score ≤2, and previously received at least one prior therapy (including at least one CD20 monoclonal antibody–containing regimen).

Patients were treated with umbralisib 800 mg daily until either disease progression or unacceptable toxicity.

As of October 20, 2018 (data cutoff), 69 patients (median age = 67 years; range = 34-81 years) were enrolled in the trial. Dr. Fowler reported data from 38 patients who had at least six months of follow-up. Of these, patients had extranodal (n=23), nodal (n=8), or splenic (n=7) disease.

Participants had received a median of two prior systemic therapies (range = 1-5 therapies); seven patients (18%) received single-agent rituximab and 26 (68%) received at least one CD20 monoclonal antibody–containing regimen.

During a median follow-up of 9.6 months, the overall response rate was 55%, including four complete responses and 17 partial responses. Another 11 patients (29%) achieved stable disease.

Overall, the median time to an initial response to therapy was 2.7 months (range not reported). The median duration of response was not reached at data cutoff (range = 8.4 months to not reached), and the 12-month progression-free survival rate was 71%.

The authors also reported that 91% of patients who had at least one post-baseline assessment experienced reductions in tumor volume.

The most common adverse events (AEs; reported in ≥20% of patients) included:

  • diarrhea (45%)
  • nausea (29%)
  • fatigue (26%)
  • headache (26%)
  • cough (24%)
  • decreased appetite (21%)

The most frequently reported grade 3/4 AEs included neutropenia (8%), febrile neutropenia (5%), and diarrhea (5%). As of data cutoff, 16 patients discontinued therapy due to progressive disease (n=7; 18%), AEs (n=3; 8%), patient decision (n=3; 8%), or physician decision (n=3; 8%).

The observed AEs “are to be expected with this class of drugs,” and did not appear to worsen with prolonged exposure to the study drug, said Dr. Fowler.

The findings are limited by the small patient cohort, short duration of follow-up, and lack of a comparator arm. Dr. Fowler noted that the researchers are continuing to follow patients to establish the long-term activity and side effects of umbralisib.

The authors report relationships with TG Therapeutics, which sponsored the trial.


Fowler NH, Samaniego F, Jurczak W, et al. Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: a multicenter, open-label, registration directed phase II study. Abstract #CT132. Presented at the American Association for Cancer Research Annual Meeting, April 1, 2019; Atlanta, GA.