Matthew S. Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist, Dana-Farber Cancer Institute; and an assistant professor of medicine at Harvard Medical School, discusses the potential utility of moving the combination of ibrutinib (Imbruvica) and umbralisib into the frontline setting of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).

Findings from a phase 1/1b study presented during the 

2020 European Hematology Association Annual Congress

 showed that ibrutinib/umbralisib elicited high response rates in CLL and MCL with a tolerable safety profile.

Updated data from the study revealed that progression-free survival and overall survival did not differ significantly from ibrutinib monotherapy in patients with MCL; however, outcomes were not negatively impacted.

In CLL specifically, the combination may have utility in the post-venetoclax (Venclexta) patient population as venetoclax is being used earlier in treatment, explains Davids.

Moving PI3K inhibitors into the frontline setting has been met with some challenges such as increased immune-mediated toxicities, says Davids.

As umbralisib appears to be a well-tolerated PI3K inhibitor, this combination may have potential utility in CLL, concludes Davids. 

Videos

Matthew S. Davids, MD, MMSc, discusses the potential utility of moving the combination of ibrutinib and umbralisib into the frontline setting of chronic lymphocytic leukemia and mantle cell lymphoma.



Dr. Davids on the Potential Utility of Frontline Ibrutinib/Umbralisib in CLL and MCL

Matthew S. Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist, Dana-Farber Cancer Institute; and an assistant professor of medicine at Harvard Medical School, discusses the design of the UNITY trials in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).

Due to the significant toxicity of combining a SIK inhibitor with a PI3K inhibitor, UNITY-CLL evaluated umbralisib, an investigational oral PI3K delta inhibitor, plus ​the BTK inhibitor ibrutinib (Imbruvica) in patients with CLL was used in this analysis, says Davids. The same combination is being evaluated in patients with MCL in the UNITY-NHL trial.

The objective of the trials ​was to ​show that dual blockade of the B-cell receptor pathway could be done effectively while maintaining a manageable toxicity profile, David​s explains. 

The studies each enrolled 21 patients with relapsed/refractory CLL and MCL, says Davids. Some patients received prior ibrutinib monotherapy; however, they were not refractory to the BTK inhibitor, Davids concludes.

Matthew S. Davids, MD, MMSc,  discusses the design of the UNITY trials in patients with relapsed/refractory chronic lymphocytic leukemia and mantle cell lymphoma.

   Dr. Davids on the Design of the Phase 3 UNITY Trials in Relapsed/Refractory CLL and MCL

Matthew S. Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist, Dana-Farber Cancer Institute; and an assistant professor of medicine at Harvard Medical School, discusses the potential utility of ibrutinib (Imbruvica) in combination with umbralisib (TGR-1202) in patients with mantle cell lymphoma (MCL) or relapsed/refractory chronic lymphocytic leukemia (CLL).

According to a recent press release, the combination of umbralisib and ublituximab demonstrated encouraging results in the phase 3 UNITY-CLL study, says Davids. Umbralisib appears to be moving towards regulatory approval in CLL and ​possibly MCL.

Although the regimen may have future utility as an off-label option, additional data is needed from larger, randomized studies, Davids explains.

Notably, ​the phase 1/1b study (NCT02268851) of umbralisib/ibrutinib was the first to show the feasibility of a BTK inhibitor in combination with a PI3K inhibitor in CLL and MCL. This approach may be beneficial in other non-Hodgkin lymphomas in the future, Davids concludes.

Matthew S. Davids, MD, MMSc, discusses the potential utility of ibrutinib in combination with umbralisib in patients with mantle cell lymphoma or relapsed/refractory chronic lymphocytic leukemia.

Dr. Davids on the Potential Utility of Ibrutinib/Umbralisib in MCL and CLL

Matthew S. Davids, MD, Associate Director, Dana-Farber Cancer Institute Center for Chronic Lymphocytic Leukemia, discusses a study that explored optimizing checkpoint blockade as a treatment for relapsed hematologic malignancies after allogenic hematopoietic cell transplantation.

This is a very challenging area, because patients have limited options, Davids says. Overall survival is typically poor — in the range of 6 months or less.

In previously published results, ipilimumab (Yervoy) was shown to induce responses in patients with lymphoid and myeloid malignancies in this patient population. At the ASH Annual Meeting, Davids presented updated results to show the long-term follow-up for these patients. Findings showed the median overall survival is 28 months, which is significantly longer than patients treated with traditional therapies.

Matthew S. Davids, MD

Articles

Dr. Davids on the Potential Utility of Frontline Ibrutinib/Umbralisib in CLL and MCL

Dr. Davids on the Design of the Phase 3 UNITY Trials in Relapsed/Refractory CLL and MCL

Dr. Davids on the Potential Utility of Ibrutinib/Umbralisib in MCL and CLL

Dr. Davids on Checkpoint Blockade Inhibition in Hematologic Malignancies After Stem Cell Transplant