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One-Size-Fits-All Approach Not Applicable in MCL

Jason Harris
Published: Friday, Sep 07, 2018

Bijal D. Shah, MD

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?

Shah: 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.




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