Ibrutinib and venetoclax combination therapy for mantle cell lymphoma: are two better than one?

Introduction: Mantle cell lymphoma (MCL) is a non-Hodgkin B-cell lymphoma typically regarded as incurable with standard chemotherapy. Ibrutinib has become an accepted second-line treatment for relapsed or refractory MCL. Although venetoclax has shown activity against the disease, these results have not been consistently seen in the post-ibrutinib era. Therefore, there is growing evidence that supports using ibrutinib and venetoclax together in patients with chronic lymphocytic leukemia.

Areas covered: This article looks at the evidence for combining ibrutinib and venetoclax in treating relapsed or refractory MCL, particularly from the AIM and SYMPATICO studies. The phase II AIM study evaluated the ongoing combination of ibrutinib and venetoclax following a run-in period of ibrutinib. The phase III SYMPATICO study started both drugs without a run-in period and included a fixed two-year duration of venetoclax.

Expert opinion: The combination of ibrutinib and venetoclax has shown effectiveness in patients with relapsed/refractory MCL, indicating potential for fixed-duration therapy. The emerging use of measurable residual disease and molecular data may help identify which patients are suitable for stopping treatment. As new information becomes available on ibrutinib in first-line settings and chimeric T-cell therapy, the optimal timing for combining ibrutinib and venetoclax may require further refinement.