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Kahl Looks Toward the Future in MCL

Angelica Welch
Published: Monday, Aug 13, 2018

Brad S. Kahl, MD

Brad S. Kahl, MD
The treatment landscape of mantle cell lymphoma (MCL) has seen several advances in the last few years, but curative strategies are still an unmet need in this uncommon malignancy, said Brad Kahl, MD.

, Kahl, a professor in the Department of Medicine, Washington University School of Medicine in St. Louis, Siteman Cancer Center, discussed the exciting new advancements on the horizon for the treatment of patients with MCL.

OncLive: What is the biggest unmet need in the treatment of patients with MCL?

Kahl: The biggest unmet need for MCL is that we don't cure it. We need curative strategies for MCL so we do not have this relentless disease with this continuation of relapse and needing subsequent salvage therapy. We would really like to improve outcomes in the frontline setting. There are a lot of novel targeted agents that are showing good activity in MCL, such as ibrutinib, acalabrutinib (Calquence), and venetoclax. A lot of us who do research in MCL are very interested in combining these promising targeted agents with our standard therapies to see if we can improve outcomes through that strategy.  

Could you discuss the work being done with ibrutinib in MCL?

In MCL, ibrutinib is currently approved for relapsed disease, and it gets a lot of use in the relapsed setting. It is being tested now in the frontline setting. There is a large trial called the SHINE trial, in which older patients with MCL who are ineligible for stem cell transplant were randomized to receive either BR or BR and ibrutinib. Ibrutinib was given throughout the 6 months of induction therapy, but then it was also continued as a postremission therapy. The SHINE trial is fully enrolled, but we do not have any readout yet from that trial. If it is a strongly positive trial, it has the potential to change the standard of care in frontline MCL, at least for older patients.

What about the potential for chimeric antigen receptor (CAR) T-cell therapy in MCL?

CAR T cells have a lot of potential in MCL. As I mentioned, MCL is not curable right now, so eventually, all patients relapse and need therapy in the second-, third-, and fourth-line settings. Ibrutinib and acalabrutinib are very effective, but their benefit is finite. They do not work forever. We really need more options for relapsed MCL, so I am hopeful that CAR T-cell therapy will be another good option for patients with MCL. We do not know yet, because there is just not enough data, but it is a very promising strategy. In 1 or 2 years from now, we will likely know a lot more about CAR T-cell therapy in MCL. 
Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018; 378:1211-1223. doi: 10.1056/NEJMoa1715519.

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