Transcript

Dr Horwitz: I'd like to welcome everyone to an Oncology Learning Network program discussing the impact of the ECHELON-2 trial in T-cell lymphoma.

My name is Steven Horwitz. I'm a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. It's my distinct pleasure to be joined today by Dr Barbara Pro, medical oncologist with an expertise in T-cell lymphoma from Northwestern University, and my colleague, Dr Alison Moskowitz, a medical oncologist, also with an expertise in T-cell lymphoma, from Memorial Sloan Kettering. Welcome, both.

Dr Pro: Thank you for the opportunity.

Dr Horwitz: I thought we'd start talking a little bit about T-cell lymphoma in general, the landscape and some of the challenges. We'll focus mostly on therapy and some of the real challenges in T-cell lymphoma, things that we deal with every day-to-day, maybe some examples.

Barbara, do you want to start off?

Dr Pro: Yeah, sure. You can share my same experience. The major challenge with T-cell lymphoma is that these are very rare diseases, and they are not the same disease, even though they are categorized as mature T-cell lymphoma, so the challenge is making the diagnosis.

It's not uncommon patients are referred to us with one diagnosis, and then upon review of the slides, we actually have a different opinion about the diagnosis.

It's really key that these patients are referred to centers where there is expertise and there is a team of not only physicians, but also pathologists to deal with these rare diseases.

The other challenge we have is that, historically, we have used treatments that are similar to treatments used during aggressive B-cell lymphoma.

Unfortunately, outcomes have been very poor, in terms of both the progression-free survival and overall survival. This really underscores the urgent need to find more effective therapies for patients affected by these diseases.

Dr Horwitz: Could you describe what typical, upfront approach might be that you would use for T-cell lymphoma off-protocol?

Dr Pro: Off-protocol, historically, we have used CHOP or a CHOP with the addition of etoposide in younger patients. As you well know, there is no randomized data looking at the comparison between these two regimens, although there is some data, mainly from Europe, looking at the addition of etoposide in younger patients.

In patients with the anaplastic large cell lymphoma subtype, there is a significant improvement in progression-free survival.

Based on that, we have used etoposide in younger patients, and the major goal will be to achieve complete remission. Historically, we have used stem cell transplantation and autologous stem cell transplantation for consolidation in patients who were eligible and considered fit for stem cell transplantation.

Dr Horwitz: Alison, we all practice similarly, so we can talk about how we do things, and then maybe highlight some of the differences that we know other people do.

When you see a new patient with newly-diagnosed, T-cell lymphoma, and you're starting on a regimen or an approach similar to what Barbara was explaining, in your mind, what are you expecting in terms of results and outcomes? What are the things you tell a patient? What are your thoughts at that initial embarking on therapy?

Dr Moskowitz: When I'm first meeting a patient with T-cell lymphoma, I'm honestly thinking about subsequent lines of therapy if I'm going to need them. I'm already worried about the possibility that the frontline treatment may not work.

Part of that is doing molecular profiling of their baseline biopsies to look at particular possible targets that may be helpful when I'm thinking about clinical trials down the road, if the frontline treatment ends up not being successful for them.

Certainly, a good number of patients can have a successful trip with the frontline treatment. In general, we think about CHOP-like therapy alone as potentially being associated with long-term remission in maybe about 20 percent of people, and potentially, a transplant.

Although, there's no randomized studies to support this, we think it probably improves the outcomes -- at least based upon what we know from Phase II studies -- by another 20 percent.

Depending upon the specific histology of T-cell lymphoma, maybe about 40 to as many as 50 percent of people may be able to have a long-term remission with this aggressive, upfront approach, but that leaves a fair number of people who will need to be thinking about what are we going to do as our next line of therapy and going forward.

Dr Horwitz: In terms of the initial approach, just practical guidance in terms of staging and restaging when you go through and start these people on that regimen, do you have a standard way you start off? And then, interim looks or not? How do you make those decisions going forward?

Dr Moskowitz: I'm going to start with standard staging with a PET scan and a bone marrow biopsy to establish the extent of disease. Also, with peripheral blood flow, a lot of these patients do have obvious involvement of their blood, or some of them have more subtle involvement, but it's good to know a baseline.

I also have been getting baseline EBV/PCR for patients with angioimmunoblastic T-cell lymphoma. We often see that at baseline, it's often something that I'm able to track throughout their treatment.

Over the course of six cycles of CHOP-based therapy, I will get a repeat PET scan, after about three to four cycles of treatment. I often get it a little earlier after three cycles only because I'm aiming to try to get them to a transplant. I want to know fairly early on how things are going, and I want to get them in with a transplant doctor, if that's our ultimate plan.

I'm hoping at that point that their PET scan will be normal, the disease will have resolved. We have found that that's associated with fairly favorable outcomes with an autologous stem cell transplant consolidation.

We have no data to change therapy or to make alterations at that point, so what I'm looking for is that the patient does not at that point have refractory disease or progressive disease.

Those findings would certainly be reason to repeat a biopsy and likely change course. I'm really at that point just confirming that they're responding to the treatment, so that we can continue on.

Dr Horwitz: Barbara, similar approach, in terms of restaging? How do you make the transplant decision or individualize that? Or is it that's pretty much a default recommendation? How do you explain that to patients?

Dr Pro: Given that the data from retrospective study, we really need to improve the outcome. I feel like I have that conversation right away, the first time I meet the patient. I do initiate interferon for stem cell transplantation at the same time.

I explain that although we do not have randomized data that looks at the very important question, whether or not stem cell transplantation should be done after achieving a CR for all patients with T-cell lymphoma, I think we had data to support the autologous stem cell transplantation does include progress-free survival.

I do feel that we have to have that conversation with the patient right away. With the exception, as we all know, of patients with ALK-positive and anaplastic large-cell lymphoma with no adverse features, I do recommend the stem cell transplantation for our patients with T-cell lymphoma.