In Search of Targeted Therapies for T-Cell Lymphoma

Cleveland Clinic researchers are working internally and collaborating with other institutions to better understand the molecular basis of T-cell lymphoma so that they can develop new drugs for the disease.

Developing treatment regimens for T-cell lymphoma has been challenging for the scientific community because of the limited number of available study participants and the inability to identify the molecular pathways that lead to the disease.

Because T-cell lymphoma is so rare (it constitutes only 10 to 12 percent of all non-Hodgkin lymphomas), it’s difficult to conduct clinical trials so that targeted therapies can be developed. “As of now, there’s no real standard of care for T-cell lymphoma, so we’ve been extrapolating data from B-cell lymphoma to treat it,” says Cleveland Clinic oncologist Deepa Jagadeesh, MD. Treatment outcomes thus far have been poor.

T-cell lymphoma also has multiple subtypes. Although peripheral T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic lymphoma and cutaneous T-cell lymphoma are the most common subtypes, there are many others. “T-cell lymphoma is such a heterogeneous disease that developing a single treatment to manage every subtype is challenging,” Dr. Jagadeesh says.

Clinical Trials

Cleveland Clinic is currently participating in a multi-center randomized, double-blind, placebo-controlled, phase 3 study of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone(A + CHP) versus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in the frontline treatment of patients with CD30-positive mature T-cell lymphomas.

Brentuximab vedotin is an antibody-drug conjugate that is currently being used to treat Hodgkin lymphoma and anaplastic large-cell lymphoma. It binds to CD30, causing the release of monomethyl auristatin E (MMAE), which arrests the growth of cancer cells, leading to cell death.

The study’s goal is to compare the progression-free survival as determined by an independent review facility between the two treatment arms. Patients with newly diagnosed CD30-positive mature T-cell lymphomas (per the Revised European- American World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues) are eligible to participate if they meet the additional inclusion criteria.

A second clinical trial in the relapsed refractory setting will begin in the next few months.

Tumor Sample Studies

In addition to the clinical trials, Cleveland Clinic researchers are collecting tumor samples for study. “One of the things we’re doing is trying to identify specific mutations so we can identify new drugs that might be effective,” says Dr. Jagadeesh. “We’re also trying to create cell lines so that we can do pre-clinical studies. If we can identify certain pathways and points where the disease becomes malignant, we can try to come up with new drugs to target those areas, and will also be able to open more clinical trials.”