Therapies and Challenges in the Evolving Treatment of Mantle Cell Lymphoma

While it is an exciting time for the treatment of mantle cell lymphoma (MCL), challenges still remain, according to Andre Goy, M.D., MS.
BY Alexandra Guadagno
PUBLISHED March 15, 2019
While it is an exciting time for the treatment of mantle cell lymphoma (MCL), challenges still remain, according to Andre Goy, M.D., MS.

CURE’s sister publication, OncLive, sat down with Goy, who is the chief of the Division of Lymphoma and chairman and director at the John Theurer Cancer Center, at the 2019 International Congress on Hematologic Malignancies, as he discussed options and challenges in the treatment landscape of MCL.

OncLive: Can you discuss treatment options for patients with MCL?
Goy: Typically, MCL needs to be recognized for its many differences and subsets. Certain conditions need to be monitored over time and for quite a while. Over time, the disease can transform aggressively, but these patients can be monitored and now treated early on.

One of the most important factors for successful treatment of classic MCL is the fitness and age of the patient. The patients can receive cell therapy and (Rituxan [rituximab]) combined induction. These patients typically do really well. Maintenance is also a benefit in younger patients. In the older patients, adding Imbruvica (ibrutinib) and Calquence (acalabrutinib) to the data is pending. The result is very impressive in terms of survival advantage, so it is an option for older patients. 

In patients where we are able to find p53 mutation at baseline, I don't think they should receive chemotherapy up front. We use Imbruvica and (Rituxan) as a window of opportunity, followed by chemotherapy consideration.

In patients who are frail and not eligible for chemotherapy, it is probably better not to give chemotherapy (right away). We are moving towards doublet and triplet exploring clinical trials, and Venclexta (venetoclax) and Imbruvica, for example, in a relapsed setting where the activity was so impressive, is in ongoing trial as we speak. This is a really exciting time in MCL, where we are really identifying the subjects who are high risk and should receive biologics before chemotherapy. The patients who are frail that can't get chemotherapy can also receive different regimens.

What are the challenges still facing this population?
There are still a number of challenges that we face in MCL. The median age at diagnosis is mid-to-late 60s, which may be difficult to treat with intensive therapy. We still don't know if high-dose therapy auto is beneficial after induction therapy. Achieving a deep response early in treatment is critical in patients with MCL. This is being looked at in the French TRIANGLE study, which is replacing stem cell transplant with Imbruvica maintenance following standard induction therapy to determine if we need to do high-dose therapy. Another obstacle with the research is in patients with blastoid variant, highly proliferative disease and p53 mutations. These patients typically do poorly, but the ZUMA-2 trial has shown promising early data in treating this population with CAR-T therapy. 

What agents look most promising for the treatment of MCL?
BTK inhibitors, including rituximab, are looking very impressive. The Venclexta/Imbruvica combination is moving towards the frontline. Our data is very impressive even in the relapsed setting. 

What are the key takeaways about MCL?
The field is changing. It is important to refer patients to clinical trials to give them access to the best options. It is important that the field is going to move towards (minimal residual disease) as well. 
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