Dr. Fenske on the Future of Daratumumab in MCL

Timothy Fenske, MD, MS, associate professor, Medical College of Wisconsin, discusses the future of daratumumab (Darzalex) in mantle cell lymphoma (MCL).

Daratumumab has not shown as much promise in lymphoma as it has in other malignancies, explains Fenske. In T-cell lymphomas, some anecdotal activity has been observed with daratumumab. In most B-cell lymphomas, however, there hasn't been a lot of activity seen with this agent, even though some of these lymphomas express CD38. It is unclear why daratumumab has shown greater success in plasma cell disorders rather than in B-cell malignancies, says Fenske.

In MCL, patients tend to have a high proportion of genomic instability, chromosome complex karyotypes, p53 mutations, and other factors that promote drug resistance. However, over the years, there has been an undoubtable improvement in survival in MCL with slow but sure successes, more so in the frontline setting than anywhere else, adds Fenske.

With some of the more aggressive induction strategies, physicians are seeing 8- to 10-year first remissions. Once a patient relapses, the disease becomes increasingly difficult to manage, after which remissions range from 1- to 2-years. Notably, long-term follow-up with acalabrutinib (Calquence) has shown remissions in the range of 2 years, further attesting to the slow but sure progress in the paradigm, concludes Fenske.