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PTCL FAQs
PTCL Management: Expert Responses to Frequently Asked Questions

Released: February 07, 2020

Expiration: February 05, 2021

Steven M. Horwitz
Steven M. Horwitz, MD
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This ClinicalThought commentary features a selection of questions asked by participants during an ASH 2019 satellite symposium focused on the optimal management of patients with peripheral T-cell lymphoma (PTCL), with responses provided by members of the program faculty.

Is it justifiable to use brentuximab vedotin in patients with very low CD30 expression?
In the ECHELON-2 study, the minimum cutoff defined as positive CD30 expression was 10% for frontline use of brentuximab vedotin. It was reproducible on central review and my understanding is that it has been quite reproducible elsewhere. I think the worry would be that for a CD30 expression level of 1% or 2%, the data might be less reproducible, but we do not have those data.

Our data with single‑agent brentuximab vedotin is that CD30 at low expression levels probably do not matter that much; for example, the Stanford CTCL study by Kim and colleagues showed responses at all CD30 levels, with lower response rates in patients with very low CD30 expression. If you are going to use something other than CHOP in frontline anaplastic large-cell lymphoma (ALCL) and you have CD30 positivity, I think it is reasonable to act on that and include brentuximab vedotin, based on the ECHELON-2 study results. Adding etoposide is the other modification for which there are some data as also being potentially helpful.

Outside of a clinical trial, given the OS benefit in the intention-to-treat population in ECHELON-2, I would at least seriously consider including brentuximab vedotin in patients with CD30 expression at any level unless I had an alternative strategy that I preferred.

Is brentuximab vedotin plus chemotherapy as initial therapy a better approach than CHOP as initial therapy followed by brentuximab vedotin salvage therapy for patients with ALK-positive ALCL?
The randomized data in ECHELON-2 show higher OS by adding brentuximab vedotin to CHP therapy vs CHOP therapy alone. Patients with ALK-positive ALCL are often younger patients, so in most cases, we are aiming for a cure. I do not think it would be appropriate or in the patient’s best interest to omit brentuximab vedotin as part of initial therapy in these cases.

What are your thoughts about ALK inhibitor therapy in the young, poor‑risk ALK‑positive ALCL patient or in relapsed patients as a bridge to transplant?
The experience with crizotinib is very limited, but in some small datasets, it appears to be an effective treatment strategy in patients who have progressed after earlier systemic therapies, and it is usually very well tolerated. The concern with ALK inhibitors is if patients are in CR, you can use it as a bridge to transplant. But if you use it as therapy without transplant, the experience in pediatric patients has been that when you stop crizotinib therapy, patients progress. So in the relapsed setting, it is active but probably not curative. For frontline ALK‑positive ALCL, we are currently awaiting data from an ongoing trial with the Children’s Oncology Group using ALK inhibitors plus chemotherapy vs brentuximab vedotin plus chemotherapy (currently suspended for evaluation of current enrollments).

Which is the best therapy for relapsed T-helper follicular lymphoma?
T-helper follicular lymphoma is related to angioimmunoblastic T-cell lymphoma, so it may benefit from similar treatment strategies. HDAC inhibitors are a reasonable option or brentuximab vedotin if there is positive CD30 expression. Clinical trials with hypomethylating agents, HDAC inhibitors, duvelisib, or cerdulatinib should also be considered.

Would you consider frontline autologous transplant for select patients with ALK‑positive ALCL, such as those with an International Prognostic Index of 4?
There are patients with very aggressive ALK‑positive ALCL that is very difficult to salvage in the relapsed setting, particularly patients with high International Prognostic index scores, where PFS may be ≤ 50% with standard therapy. In such cases, I will make a referral for autologous transplant and discuss the advantages and disadvantages with those patients. These are often young patients who are likely to tolerate and may benefit from autologous transplant.

What is the benefit of transplant in first remission for patients with NK T‑cell lymphoma?
It depends on the patient; there are few definitive data to guide us here. This is a disease in which radiation therapy is very effective, so the first choice would be to use radiation therapy after induction chemotherapy. In cases where patients have more aggressive and advanced disease, they may be candidates for autologous or, in some cases, allogeneic transplant.

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