A Conversation About Peripheral T-Cell Lymphoma with Dr. Ranjana Advani

Saul Rosenberg Professor of Lymphoma at Stanford University Medical Center

Would you briefly describe peripheral T-cell lymphoma?

There are many different entities that make up the broad category of peripheral T-cell lymphoma (PTCL). At the broadest level, PTCL is characterized as nodal or extranodal, and there are at least 15 different subtypes.

PTCL is rare, and, among the types, there is a lot of geographic heterogeneity. For example, the most common PTCLs in the United States are not the same as those most commonly diagnosed in Asia or Europe.

How common is PTCL? 

PTCL accounts for approximately six percent of all non-Hodgkin lymphomas.

How is PTCL typically treated?

Because PTCL is rare, there are very few randomized clinical trials conducted to help guide treatment decisions. The principles of treatment of PTCL have largely been extrapolated from treatment paradigms developed for B-cell lymphomas.  There are certain subtypes of PTCL for which there are recommended treatments.  For example, there’s an entity called extranodal NK/T-cell lymphoma for which CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), the standard therapy used to treat B-cell lymphomas, is not an effective treatment. Asparaginase-based regimens or methotrexate-based regimens are used with radiotherapy to treat extranodal NK/T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma or PTCL, not otherwise specified are treated like a B-cell lymphoma.

There are more recent treatment regimens, such as those that incorporate etoposide (Etopophos or VePesid into CHOP regimens (CHOEP), that appear to improve outcomes compared with CHOP alone in some patients with PTCL; however,  there are no data from randomized prospective clinical trials to support these findings.

There are currently various novel agents, including brentuximab vedotin (Adcetris), a very specific-targeted antibody-drug conjugate of CD30, that has shown an 80 percent response rate in patients with relapsed anaplastic large cell lymphoma which is CD30 positive. The drug is currently being investigated as frontline therapy in other subtypes of T-cell lymphoma.

What are the current main areas of research?

There are two main research questions being asked. The first question is what is the best frontline therapy? Which chemotherapy or novel agent added to chemotherapy will improve outcomes in patients?  For example, adding brentuximab vedotin (Adcetris) to chemotherapy shows promise for patients with anaplastic large cell lymphoma, which expresses CD30, and about 30 percent of other PTCLs also express CD30 , and may similarly see improved outcomes with this therapy. Pralatrexate (Folotyn) and romidepsin (Istodax),  are novel agents being investigated as frontline therapy in combination with chemotherapy.

The second question is whether or not a transplant should be done for patients in remission and if so, should it be an autologous or allogeneic transplant? The Europeans are testing the addition of alemtuzumab (Campath) to a CHOEP-like regimen, and comparing the results after autologous versus an allogeneic transplant.

There is a fair amount of research going on; there are three approved novel agents:  brentuximab vedotin (Adcetris), pralatrexate (Folotyn) and romidepsin (Istodax); there are drugs in the pipeline for relapsed PTCL; and there are other agents being developed. The lack of a large data bank with a tissue repository of the numerous different subtypes of PTCLs to investigate what is happening at the molecular level presents a challenge for researchers. Information about what is causing molecular changes helps to guide the development of specific agents to treat diseases and these efforts need more support.

Please discuss the importance of clinical trials.

I think that every patient with PTCL should enroll in a clinical trial. The T-cell Consortium has just completed enrollment of a trial of frontline treatment, and there are other ongoing trials.  Because PTCL is so rare, and there is no standard of care, the only way to improve care for patients is through clinical trial data. Patients should investigate whether or not they are eligible for a clinical trial. I encourage all community oncologists with T-cell lymphoma patients to reach out to an academic center to determine if a clinical trial is available. We often receive phone calls from community physicians asking, “We have a newly diagnosed T-cell patient, what should we do, or would you see the patient?”  I often present American Society of Hematology (ASH) lymphoma updates and use email communication of key trials to establish relationships with community physicians. Within my referral base there is great collaboration which is so terrific, and we’ve certainly seen medical advancements as a result of that team work.

Are there any new and emerging therapies you wish to discuss?

A drug called alisertib (MLN8237), which is an aurora kinase inhibitor, is still undergoing clinical trials and has shown some activity in Phase I for treating T-cell lymphoma. A larger Phase II trial is ongoing for relapsed disease. If the results remain positive, alisertib will have to be studied in combination with chemotherapy, then investigated as frontline therapy.

How are you involved with the Lymphoma Research Foundation (LRF), and why would you recommend that a patient become involved with LRF?

I participate on the Scientific Advisory Board for LRF, and have volunteered as a speaker at patient education symposia

Lymphoma is complex and T-cell lymphomas are even more complex, so patients need a reliable resource. I actually suggest to my patients that if they want to look up information, to go to the LRF’s website. LRF has been a leader in helping lymphoma patients and advancing lymphoma research.

Updated April 24, 2013