Bijal D. Shah, MD
The current state of treatment for patients with mantle cell lymphoma (MCL), continues to be challenging, according to Bijal D. Shah, MD.
MCL accounts for about 6% of all NHL diagnoses in the United States, and high-risk patients comprise 10% to 15% of MCLs. An analysis of the National Cancer Institute SEER database showed an age-adjusted annual incidence of 1.01 per 100,000 population from 1995 to 2013, with a steady annual increase of 2.56%.1
The FDA has approved a number of agents to treat patients with MCL since the late 1990s including rituximab (Rituxan), bortezomib (Velcade), temsirolimus (Torisel), bendamustine, lenalidomide (Revlimid), ibrutinib (Imbruvica), and acalabrutinib (Calquence). As a result, the risk for MCL-specific death declined significantly from 1995 to 1998 and again from 2009 to 2013 (HR, 0.58; 95% CI, 0.53-0.81).2
However, only patients with advanced disease demonstrated a significantly reduced risk for death (P
<.0001) from SEER data sets.
Nonetheless, Shah, an associate member in the Department of Malignant Hematology at Moffitt Cancer Center, who delivered a presentation at the OncLive®
State of the Science Summit™ on Hematologic Malignancies, said physicians and investigators are struggling to advance the field, in part because novel therapies are rarely evaluated in MCL-specific trials.
In an interview with OncLive
, Shah discussed the challenge of treating this highly heterogeneous disease, how to choose the optimal treatment regimen, and the ongoing role of BTK inhibitors.
OncLive: How would you currently describe the state of MCL treatment?
MCL is a clinically and genomically heterogeneous disease. One of the reasons I first got excited about MCL is that it's a very rare lymphoma. I thought I could figure this out and contribute something major, because how much variability can there be in this one lymphoma that makes up 6% to 8% of B-cell lymphomas? I learned very quickly that there is quite a bit of variability, in fact. One of our first papers was a review paper titled, “Mantle cell lymphoma is a clinically heterogeneous disease.” That's the first thing I would want people to take home: there is no one-size-fits-all [approach].
We are starting to learn those features that drive a worse outcome. Whether we talk about this in terms of the Mantle Cell Lymphoma International Prognostic Index (MIPI) or whether we talk about this genomically, when you look at high-risk patients, they are typically more proliferative and also commonly carry these P53
mutations. This was very nicely described by the MCL35 assay. This gene-expression profiling tries to capture more proliferative versus less proliferative MCLs, and then overlap that with the MIPI and the combined MIPI (MIPI-c), which includes a measure of Ki-67 and P53
mutation status. It's highlighting this intersection of the clinical presentation and the biological behavior.