Moving Forward With Ibrutinib Plus Venetoclax in MCL


Matthew Matasar, MD, discusses the next steps for the development of ibrutinib given in combination with venetoclax for patients with mantle cell lymphoma, and potential challenges with using the combination.

Matthew Matasar, MD, chief of the division of blood disorders at the Rutgers Cancer Institute and professor at the Rutgers Robert Wood Johnson Medical School, discusses the next steps for the development of ibrutinib (Imbruvica) given in combination with venetoclax (Venclexta) and potential challenges with using the combination.

Ibrutinib with venetoclax was compared with ibrutinib and placebo for the treatment of patients with relapsed/refractory mantle cell lymphoma in the phase 3 SYMPATICO study (NCT03112174). The combination therapy appears well-tolerated, opening possibilities for exploring other combinations, particularly in relapse settings, and potentially moving them to first-line treatment.

Here, Matasar emphasizes the importance of ongoing data analysis and patient follow-up in treating MCL, suggesting that understanding long-term outcomes and responses to various therapies will help clarify the efficacy of combining different treatments, such as the doublet mentioned.


0:09 | Most importantly, we need to continue to follow these data and watch them mature. Mantle cell lymphoma is sometimes a marathon and not a sprint and following these patients to learn their subsequent outcomes, impact of the next line of therapy, and responses to the next line of therapy will better clarify the impact of having a doublet in this clinical context. The combination was very well-tolerated with no new safety signal outside of that which is expected from its constituent components. That certainly does give us an opportunity to think about other combinations both in relapse setting as well as whether they're optimal partners. to enhance their activity and enable it to move to the first-line setting.

0:46 | One challenge in this field is that we have a number of [Bruton’s tyrosine kinase (BTK)] inhibitors that are available currently. When SYMPATICO was designed, it leveraged ibrutinib, which was an even more relevant consideration because of a relative paucity of alternatives. Now, we find the therapeutic landscape with multiple approved BTK inhibitors, both covalent and noncovalent. It remains an interesting question for us in the community of lymphoma doctors, whether ibrutinib or other BTK inhibiting approaches may be the optimal partner for venetoclax.

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