Ibrutinib plus Venetoclax May Be Effective in Mantle-Cell Lymphoma

In patients with mantle-cell lymphoma the BTK inhibitor ibrutinib and the BCL2 inhibitor venetoclax each have antitumor activity as monotherapies, with each achieving complete response rates of 21%. Preclinical studies suggest that combination treatment with ibrutinib and venetoclax may be synergistic and achieve superior responses compared with either monotherapy. Tam and colleagues assessed the safety and efficacy of ibrutinib plus venetoclax in an open-label phase II trial in 23 patients with relapsed or refractory mantle-cell lymphoma and 1 patient with previously untreated mantle-cell lymphoma. The primary endpoint was complete response rate at week 16, and the response was compared with historical controls. The complete response rate at 16 weeks was 42% according to computed tomography and 62% according to positron-emission tomography, indicating superior efficacy compared with monotherapy, and 78% of responding patients exhibited durable responses ongoing at 15 months. Further, minimal residual disease clearance was confirmed in 16 of 19 (84%) patients by flow cytometry and 9 of 16 (56%) patients by allele-specific oligonucleotide polymerase chain reaction. Combined treatment with ibrutinib plus venetoclax had an acceptable safety profile, although serious adverse events occurred in 14 patients (58%). Collectively, these findings suggest that combined treatment with ibrutinib and venetoclax is more effective than either single-agent therapy in patients with mantle-cell lymphoma. These results support further clinical investigation of ibrutinib plus venetoclax, and a phase III trial is currently under way.

Tam CS, Anderson MA, Pott C, Agarwal R, Handunnetti S, Hicks RJ, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med 2018;378:1211–23.

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