Peripheral T-cell lymphoma accounts for about 7% of all non-Hodgkin lymphoma cases. Over the last decade, new drugs have emerged for this condition, with new findings on some of these presented at the recent 2019 American Society of Hematology annual meeting.
In this exclusive 乌鸦传媒 video, , director of the Center for Lymphoid Malignancies and co-program director of the Lymphoid Development and Malignancy Program in the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center in New York City, discusses the exciting new trials.
Following is a transcript of his remarks:
The T-cell lymphomas, the peripheral T-cell lymphomas, as most people are aware, are pretty rare diseases. According to the latest WHO [World Health Organization] classification, there are now recognized about 30 distinct subtypes of the disease. Collectively, they comprise about 6,000 to 10,000 cases per year in the United States, comprising about 10% of all cases of non-Hodgkin's lymphoma.
The most common subtype of the disease is peripheral T-cell lymphoma, not otherwise specified -- kind of a default garbage term, where those entities that don't neatly fit into the other subtypes are sort of lumped there. There are only about 2,500 cases of that particular disease.
What most physicians and trainees know well is these diseases are distinctly different in their behavior from B-cell lymphomas, which are, by far, more common, accounting for about 85% of all lymphomas. While we recognize a relatively high cure rate -- maybe 60%, 70% -- with diffuse large B-cell lymphoma, the aggressive T-cell lymphomas, in contrast, have a cure rate that might only sit at around 20% or 25% when people use conventional chemotherapies, the standard of care we recognize as CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] chemotherapy.
When you think about why patients with T-cell lymphoma do so poorly compared to their counterparts with B-cell disease, it's sort of enlightening to recognize the fact that the therapies we use in T-cell lymphomas historically are largely developed from the treatment of B-cell lymphoma and that we've never really successfully developed a discrete regimen just for patients with T-cell lymphoma. I think right now those tides are beginning to turn. In fact, since 2009, we have three new drugs that have been approved for the disease over the last decade.
While those drugs are not perfect, they actually represent interesting opportunities. They're drugs that appear to work only in T-cell lymphoma. They're not widely approved in other diseases, and now a lot of new data from our group and select others are beginning to demonstrate that combinations of these new drugs are able to produce response rates that are substantially greater than what we see with the single agents.
This has now led many groups to begin to think about using these drugs -- most of which are epigenetics or romidepsin, belinostat, and pralatrexate -- in combination with various immunologic therapies. Some of those immunologic therapies include PD-1, and there are studies now ongoing at Columbia led by Dr. Enrica Marchi and our team, who are beginning to systematically evaluate the role of PD-1 in combination. Recent data, including some data being presented here at ASH, suggests that PD-1, by itself, is only an okay drug, with a response rate of about 40% in small numbers of patients -- not really generating a lot of enthusiasm.
Brentuximab, which was approved in the disease, and now in the ECHELON-2 study in patients with mostly anaplastic large cell lymphoma, has been shown to produce a survival advantage when combined with CHP [cyclophosphamide, doxorubicin, prednisone], no vincristine, compared with CHOP chemotherapy.
I believe the future of T-cell therapies is going to largely depend upon some of these novel combinations. There may be some merit in adding these new drugs to CHOP-based chemotherapy, but as a whole, I'm not as enthusiastic nor optimistic about those prospects.
Thinking about how to tailor the new drugs to the biology, how to leverage some of the new immunotherapies -- be it antibody-drug conjugates like brentuximab, be it PD-1, be it CTLA-4, be it all sorts of other drugs and new bispecifics -- I think we're poised now to try to be a little innovative, a little creative, adding some of these new immunologic agents on these novel backbones predicated on these many new drugs that are being proved in the disease.
I would encourage doctors and patients alike to look at available clinical trials, because in my estimation, these trials are producing responses and efficacy that is a little bit unprecedented. I think it gives us all hope that we're beginning to turn this corner in T-cell lymphoma so we can improve the outcome for all patients.