PYRAMID: A Personalized Medicine Study in Lymphoma

Update: this study is closed to enrollment. 

Pyramid Trial Background

With increasing knowledge of cancer biology and availability of new drugs, it is expected that therapy will be increasingly tailored to individual patients’ tumor subtypes. Examples of this in breast cancer, colon cancer and CML have emerged over the past ten years. Often referred to as “personalized medicine” or “precision medicine”, this targeted approach to cancer therapy relies on translational research that defines a drug’s clinical activity in the context of the tumor’s cellular and genomic pathology.

Translational research has characterized the molecular basis of the clinical heterogeneity in various lymphomas, and many new agents are in development for lymphoma. Although the targeted development of these drugs in specific lymphoma patient subgroups could potentially speed their availability to the right patients, there are two major challenges to targeted trials in lymphoma. First, the empiric clinical research has led to highly active drug combinations that improve outcomes for many patients with lymphoma and in some specific types current therapy does in fact successfully treat a portion of the patients; leaving fewer patients with an unmet medical need to enter clinical trials. Second, it is a practical challenge to test and quickly identify specific lymphoma patient subgroups that can be enrolled in clinical trials of targeted drugs. Therefore a personalized study should ideally use a practical, rapid test to identify a lymphoma group that is not responsive to known treatment and test a therapy that targets an important pathway in those tumors.

Pyramid Trial Summary

The PYRAMID trial addresses both of these issues in order to test an investigational combination of R-CHOP with or without VELCADE, a known NFKB inhibitor, specifically in non-GCB lymphoma. The non-GCB subtype of DLBCL has been shown to be dependent on the NFKB pathway by numerous studies. Importantly, the NFKB pathway appears to be a major factor leading to the inferior outcomes of non-GCB (both progression free and overall survival) treated with R-CHOP therapy so there is good rationale to test NFKB inhibition in these patients. Therefore the PYRAMID study starts out by determining if a newly diagnosed patient has the GCB subtype or non-GCB subtype. Each group constitutes approximately 50% of DLBCL and the subtype results are available to the clinician in a few days. The non-GCB subtype is eligible for the PYRAMID study.

The PYRAMID study is enrolling patients at academic centers, major hospitals, and community practices across the United States, including Weill Cornell Medical College. Diagnostic pathology blocks will be reviewed at a CAP/CLIA-certified pathology lab for centralized subtyping. The pathology samples undergo non-GCB testing via a 3-marker immunohistochemistry panel, and the results are reported directly to the clinical site in a few days. All pathology blocks are returned to the clinical sites (range 4–6 business days to date). To date the non-GCB subtype represents 40% of the DLBCL patients screened, in line with previous reports.

At Weill Cornell Medical College, the principal investigator for the Pyramid study is Dr. John Leonard. To learn more about the study or to find out if you are eligible, please contact June Greenberg, RN at (212) 746-2651 or email June at

Author: lymphomaprogram

Located on the Upper East Side of New York City, the Lymphoma Program at Weill Cornell Medical College/NewYork Presbyterian Hospital is internationally recognized for our efforts to enable patients with non-Hodgkin lymphoma, Hodgkin disease and related disorders to have the best possible clinical outcome, including cure when possible.

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