Jia Ruan, MD, PhD
Long-term outcomes for T-cell lymphoma remain suboptimal, explains Jia Ruan, MD, PhD. However, ongoing studies are investigating exciting regimens—including additions to the standard CHOP regimen—that could have the potential to change practice for these patients.
For example, a phase III study is looking at the efficacy and safety of the HDAC inhibitor romidepsin (Istodax) combined with CHOP chemotherapy versus CHOP alone in patients with untreated peripheral T-cell lymphoma (NCT01796002). The randomized study, which is expected to enroll 420 patients, is using progression-free survival (PFS) as its primary endpoint and will be completed in July 2019.
Ruan, an associate professor of Hematology/Oncology at Weill Cornell Medicine/NewYork-Presbyterian Hospital, shared some of the ongoing work in the field of T-cell lymphoma and the unanswered questions investigators are still facing for these patients in an interview during the 2017 OncLive®
State of the Science SummitTM
on Hematologic Malignancies.
OncLive: What did you discuss in your lecture on T-cell lymphoma?
I see a lot of patients in our group for non-Hodgkin lymphoma (NHL) and there is 1 distinct subtype, which is T-cell lymphoma. It is not a very common subtype, it is in about 5% to 20% of patients with NHL. But, it is quite heterogeneous and also very difficult to treat. The long-term outcomes for patients with T-cell lymphoma remain suboptimal. For example, the studies generally state that it is a 5-year survival rate of about 20% to 30%, which certainly has room for improvement.
We are delivering not only standard of care, but also looking at options of clinical trials. For example, can we intensify our induction chemotherapy or can we incorporate novel biological agents so that we can improve effectiveness? We need to especially try to improve complete remissions (CRs) for patients with T-cell lymphoma.
Subsequent to that, patients could have options to move on to consolidative bone marrow transplant or they can consider maintenance strategies in order to remain in remission longer.
How does T-cell lymphoma present, and what are the characteristics of it?
Peripheral T-cell lymphoma, the most common subtype, includes angioimmunoblastic T-cell lymphoma or anaplastic large cell lymphoma. Patients with those diseases can present with very symptomatic lymphadenopathy, which is swelling of lymph nodes. They may have some fevers, constitutional symptoms like weight loss, and also a significant proportion of those patients may have skin rash and inflammatory symptoms.
Diagnosis of T-cell lymphoma can be challenging. It requires a very specialized hematopathologist—one who definitively diagnoses T-cell monoclonalities. It needs to be differentiated, excluding other types of NHL or Hodgkin lymphoma.
Overall, the chemotherapy responsiveness of T-cell lymphoma tends to be more resistant. You can sort of get glimpses of that based on historical data; with the most common therapy, CHOP, we expect overall response rates (ORRs) in the 60% to 80% range and only half of them are in CR. That basically suggests that we should be looking at alternative therapies, either chemotherapy with a different backbone or incorporating biological agents that are much more specific for T-cell lymphoma.
What ongoing research is looking at different backbones or other biological agents?
A significant amount of research is ongoing; there are more studies focusing on incorporating novel agents into CHOP. This is because physicians do have a lot of experience with CHOP and it is widely accepted. For example, there are phase III studies ongoing or in the process of waiting for data maturation incorporating an HDAC inhibitor, romidepsin. Adding romidepsin to CHOP compared with standard CHOP. Those are being performed globally, primarily in Europe. I do believe that the study has completed accrual and we are just waiting for data maturation.
Romidepsin alone has very significant clinical activity in the relapsed setting. One would assume that when you move earlier into the frontline setting, the efficacy should be quite considerable. We do have data coming from a phase I study that seem to support that.
We certainly also understand that when you combine 2 different modalities—chemotherapy plus biologic agents—you also anticipate more toxicities. In this particular combination, there are more hematologic toxicities, such as anemia, thrombocytopenia, and neutropenia. However, all of those are manageable by supportive care. The key question is, do you achieve higher CR rates and achieve higher PFS? I hope that, eventually, will translate to overall survival.