Using Combination Therapy for Patients With Relapsed/Refractory MCL

Matthew S. Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist, Dana-Farber Cancer Institute and an assistant professor of medicine with Harvard Medical School, discusses the prognosis expected for patients with mantle cell lymphoma (MCL), as well as chronic lymphocytic leukemia (CLL), in the relapsed/refractory population.

The advent of the BTK inhibitor ibrutinib (Imbruvica) certainly improved the outlook for patients with relapsed/refractory MCL and CLL, Davids says. It is an active drug, but the durability of response is relatively short among those with high-risk disease. In MCL, for example, even though the response rates are high, the progression-free survival is only a little over 1 year with ibrutinib as monotherapy.

This serves as the rationale for the development of combination approaches for this patient population, and there are a number in development now, says Davids. One combination is looking at dual blockade of the B-cell receptor pathway. It is known the CLL cells and MCL cells depend heavily on this pathway, and there is another arm of the pathway that has Pi3K as a key node, so there is interest in going after this other arm of the pathway to potentially prevent resistance to ibrutinib as a monotherapy, Davids concludes.