Potential Implications of Using Ibrutinib With Venetoclax in MCL

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 how ibrutinib (Imbruvica) given in combination with venetoclax (Venclexta) compares with ibrutinib and placebo for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL).

The combination was evaluated in the phase 3 SYMPATICO study (NCT03112174), a multinational, double-blind study which included patients with relapsed/refractory MCL who received 1 to 5 prior therapies for MCL. Once enrolled, patients were randomly assigned in a 1:1 fashion to receive ibrutinib 560 mg once daily for 24 months in combination with venetoclax or placebo.

A total of 134 patients were treated with ibrutinib plus venetoclax. Investigators evaluated the primary end point of median investigator-assessed PFS with global censoring, which was 31.9 months in the ibrutinib arm vs 22.1 months among the 133 patients in the ibrutinib plus placebo arm.

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0:09 | We see an improvement in clinical end points with the combination treatment both in terms of overall response rate, progression-free survival, and depth of response. We hope to continue to follow these patients over time and see whether this combination translates to improvements in overall outcomes and overall survival. Due to setting, relapsed/refractory mantle cell lymphoma is a moving target. We have other drugs emerging in the space, but the availability of a potent and well-tolerated oral combination approach is very attractive.

0:39 | The potential implications are that we may see a new option emerging for patients with a higher-risk of relapsed/refractory mantle cell lymphoma where we may be able to get more benefit out of our line of [Bruton's tyrosine kinase] inhibiting therapy with this combination approach, deferring the potential toxicities of other later live interventions, such as CAR [chimeric antigen receptor] T-cell therapy and allogeneic stem cell transplantation.