Steven Horwitz, MD
Though T-cell lymphoma is a more rare hematologic malignancy, researchers are exploring therapies such as brentuximab vedotin (Adcetris) to improve outcomes for these patients.
For example, the double-blind, randomized, multicenter, phase III ECHELON-2 trial is comparing brentuximab vedotin plus doxorubicin, prednisone, and cyclophosphamide (CHP) with standard CHOP as a potential frontline treatment for patients with CD30-positive mature T-cell lymphomas (NCT01777152). The primary endpoint is progression-free survival (PFS) with an estimated completion date of December 2017.
“Now, there's this constant stream of clinical trials adding to standard therapy or instead of standard therapy,” says Steven Horwitz, MD, who lectured on T-cell lymphoma during the 2016 OncLive
® State of the Science Summit on Hematologic Malignancies. “For a patient who is interested, there probably is access to something new or different if they want to try something different from the standard.”
Horwitz, an associate attending physician at Memorial Sloan Kettering Cancer Center, sat down for an interview during the meeting to discuss standard initial therapy for patients with T-cell lymphoma with a look ahead to what the community can expect next in the field.
OncLive: Can you provide an overview of your research with T-cell lymphoma?
: In my presentation, I discussed T-cell lymphoma, and highlighted what some of our standard initial approaches are, as well as some of the newer data that do not yet modify our standard approach—but maybe they will on the horizon. I also went into some newer data in relapse diseases, including a couple of subtypes, some things that were published this past fall, and a couple of more relevant abstracts from the 2016 ASH Annual Meeting that may be practice relevant, if not totally practice changing.
What are some current clinical trials that are happening in relation to T-cell lymphoma?
In terms of the upfront setting, a trial that is accrued now but we are waiting on data, is adding brentuximab vedotin to standard combination chemotherapy. This is the ECHELON-2 study, which adds brentuximab to CHP, which is a combination of doxorubicin, prednisone and cyclophosphamide. That was randomized in a double-blinded fashion against CHOP plus placebo.
It's a study with more than 400 patients, which is by far the biggest for a prospective randomized study we have in T-cell lymphoma. It's going to give us a lot of very good quality data. It just finished accrual within the past month, so data will likely be out within the next year or 2. That's probably the next thing that has the best chance of really improving, or stepping up standard of care, in patients with anaplastic large cell lymphoma, and perhaps across the board in any of the CD30-expressing T-cell lymphomas. That's pretty exciting.
Another new, ongoing study is looking at the addition of lenalidomide (Revlimid) to standard combination chemotherapy. There is another study adding romidepsin (Istodax) upfront. As we get results from those studies within the next couple of years, we are going to have a wave of studies saying, "Is something really better than CHOP?" or, "Is adding 1 of these newer drugs really making a difference for some subset of the patients?"
What abstracts from the 2016 ASH Annual Meeting could be practice changing?
There were not a ton of studies in T-cell lymphoma. There was a randomized study called the ALCANZA study, which randomized patients with cutaneous T-cell lymphoma that expressed CD30. They defined it in that study as 10% or greater. There were a couple phase II studies about brentuximab vedotin that looked promising, but this was a randomized study where, in rare diseases like T-cell lymphoma, we have very few randomized studies against standard treatments. In this case it was bexarotene or methotrexate.
There was a 100-patient study done in the United States, Europe, and Australia—really powerfully in favor of brentuximab vedotin. Therefore, the overall response rate was much higher—about 68% for the single agent—which recapitulates the small phase II studies, so there wasn't really regression in a multicenter setting.
There’s another study of the drug in which the responses were at least 4 months durable, which was the primary endpoint. That was significantly better for brentuximab vedotin. The PFS is more than 4 times better, so that drug in a big, international study looked a lot better than a lot of the other standard therapies we commonly use.