Personalizing lymphoma treatment: New study seeks better outcomes

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma in adults. While many people are cured with standard chemotherapy, outcomes vary widely depending on the biology of the disease. One subtype, known as germinal center B-cell (GCB) DLBCL, continues to pose challenges, especially for patients with higher-risk disease. 

For more than 20 years, the backbone of treatment for newly diagnosed DLBCL has been a chemotherapy combination called R-CHOP (rituximab, cyclophosphamide, doxorubicin, prednisone). More recently, a newer drug, polatuzumab vedotin, was added to a modified version of this regimen (R-CHP) and approved as a first-line treatment option.  

While this approach improved outcomes overall, patients with the GCB subtype did not experience better results compared with standard therapy. That gap highlights the need for new treatment strategies specifically designed to help this group. 

A new clinical trial is evaluating a targeted therapy called zilovertamab vedotin (MK-2140) plus R-CHP to determine if it offers improved and longer-lasting responses than polatuzumab vedotin with R-CHP.

Providence Cancer Institute is currently enrolling patients in this trial. The principal investigator is Natasha Edwin, M.D., hematologist and medical oncologist, Providence Cancer Center Oncology and Hematology Care Clinic, Westside Portland.  

Why zilovertamab vedotin? 

Zilovertamab vedotin belongs to a class of treatments called antibody–drug conjugates. These therapies are designed to deliver chemotherapy more precisely to cancer cells while limiting damage to healthy tissue. 

Zilovertamab vedotin targets a protein called ROR1, which is commonly found on the surface of lymphoma cells but is rarely present on normal adult cells. Once the drug binds to ROR1, it is taken inside the cancer cell, where it releases a potent anti-cancer agent that disrupts cell division and triggers cell death. 

Earlier phase studies showed encouraging results with zilovertamab vedotin, including strong response rates when combined with standard chemotherapy in untreated DLBCL.  

How the study works 

This is a global, randomized clinical trial enrolling nearly 600 adults with newly diagnosed GCB DLBCL who have not yet received treatment. Participants are assigned to one of two groups: 

Both treatments are given in cycles every three weeks. Patients with higher-risk disease may receive additional therapy to reduce the chance of the cancer returning.  

The main goal of the study is to see how many patients achieve no detectable cancer at the end of treatment, based on PET imaging. Researchers will also track how long patients remain cancer-free and closely monitor side effects to better understand safety. 

Why this matters 

Achieving a complete response at the end of treatment is strongly linked to long-term survival in DLBCL. By focusing on a subtype with ongoing unmet needs, this study aims to determine whether a more precisely targeted therapy can improve outcomes for patients who still face a higher risk of relapse. If successful, the results could help refine first-line treatment options and move care closer to truly personalized lymphoma therapy. 

Learn more about this study 

A Clinical Study of Zilovertamab Vedotin Plus Rituximab Plus R-CHP Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma 

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