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Combination of Ibrutinib and Buparlisib Shows Promise in MCL and other NHLs

Angelica Welch
Published: Friday, Jun 16, 2017

Connie Batlevi, MD, PhD

Connie Batlevi, MD, PhD

A phase I/Ib trial of ibrutinib (Imbruvica) and buparlisib in relapsed/refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL) is being conducted to demonstrate synergy between the BTK and PI3-kinase inhibitors.

Connie Batlevi, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discussed the trial and its implications in MCL.

OncLive: Could you provide an overview of your study?

Batlevi: The data that we are presenting here at ASCO are from the phase I dose escalation portion of the combination therapy including buparlisib and ibrutinib in MCL, FL, and DLBCL. Buparlisib is a pan-PI3 kinase inhibitor and ibrutinib is a BTK inhibitor. Both of these are given as oral drugs, daily on a 28-day cycle.

In terms of the findings of this combination, it is relatively safe—although we do see the expected toxicities associated with both drugs. For example, hypoglycemia is seen because it is a PI3K-alpha effect, although grade 3 hyperglycemias are relatively infrequent at about 10%. Other toxicities include anorexia, loose stool, as well as central nervous system effects related to the buparlisib, which include mood changes, anxiety, and depression.

What do you think the next steps would be following these findings?

We are continuing to phase Ib and phase II dose expansion cohorts in MCL, FL, and DLBCL. So, we will see where that leads. At least based on very small numbers, which is difficult to say, the overall response rate is very intriguing for MCL.

Can you speak to the synergy between ibrutinib and buparlisib?

This is based on 2 preclinical studies, one of them in large cell lymphoma and the other one was in CLL, I believe. It looked at large-scale pharmacologic data and essentially, with the combination of ibrutinib and buparlisib, the cell kill rate was higher in DLBCL compared to each individual agent alone. So, based on that evidence of synergy, it made sense to combine the two. 
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