Dr Ruan Highlights Hot Topics in the Lymphoma Space

Jia Ruan, MD, PhD, Professor of Clinical Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, highlights various hot topics being discussed in the lymphoma space.

Transcript

Hello. My name is Dr Jia Ruan. I'm a professor of clinical medicine at Weill Cornell Medicine and NewYork-Presbyterian Hospital. I'm a physician taking care of patients with lymphoma.

I want to bring up a few points. The first is that, yes, there is a growing list of single agents that are now available, either FDA approved or in extensive clinical development for T-cell lymphoma.

Currently, there are 5 novel agents in the T-cell space including antifolate pralatrexate HDAC inhibitor, romidepsin and belinostat, anti-CD30 antibody-drug conjugate, brentuximab vedotin, and an antibody against CCR4, which is mogamulizumab. There are many more agents that are really at the cusp of making a breakthrough contribution.

I just want to give some examples. Currently, there is an oral form of azacitidine being investigated in a global Phase III study to compare to investigator's choice. The results of that are eagerly awaited.

There's also a histone demethylation agent, valemetostat, and it's in early development, but there is a dedicated pivotal phase 2 study that are currently underway.

The PI3 kinase inhibitors are being extensively studied in relapsed setting and compared to other single-agent T-cell lymphoma which generally gives an overall response rate (ORR) in the 30 percent range, PI3 kinase inhibitors such as duvelisib, which is a delta-isoform inhibitor gives an ORR over 50 percent, which is a substantial improvement as a single agent. It's been studied, both as a single agent as well as in combination.

Other agents including, for example, PD-1 inhibitors, specifically for EBV-driven extranodal NK/T-cell lymphoma, which seems to have a susceptibility and therefore treatment sensitivity to those particular agents. In this regard, the single agent list is growing and we have certainly better and more effective agents in the developmental horizon.

The second point being that combination perhaps is better.

One example that I want to give, which also has been published, is that the HDAC inhibitor, romidepsin, has the modest single-agent activity 30 percent for T-cell lymphoma. When that's combined with other agents, such as lenalidomide, which is an immunomodulatory agent, the doublet actually gives an ORR over 50 percent, which is certainly improved compared with a single agent.

The proof of principle is that you can certainly have combinations that target different aspects of the pathways and to have a synergistic treatment outcomes.

The third point that I want to bring up is the combination with novel agents, and trying to move that into a first-line, frontline settings to benefit our T-cell lymphoma patients as early as possible.

An example including hypomethylation agent, azacitidine, in combination with CHOP-based chemotherapy, and we actually led the first Phase II exploratory study. We have reported our findings in last year's ASH. In fact, we will be providing update at this year's ASH for this particular combination.

The cooperative group is currently organizing a randomized study using azacitidine-plus CHOP or CHOEP and also compare that with PI3-kinase, duvelisib, plus CHOP or CHOEP, then compare with a standard arm of chemotherapy alone.

That's kind of exciting, right? The concept is we now have the option and opportunity to test if adding novel agents to chemotherapy or other novel agents in the frontline setting and really changed the treatment efficacy and continue to provide safe and effective treatment options for our patients.

I'm quite excited for all those options coming up for patients with T-cell lymphoma.

The most exciting aspect of taking care of patients with T-cell lymphoma is we are in an era where there's a lot of knowledge that's happening based on a collaborative research community from basic translational and clinical research and collaboration.

We have a better way of making diagnoses. We actually can do test not only based on morphology, cytogenetics—We can also do deep sequencing and knowing what kind of mutation profile that a patient with T-cell lymphoma might have and what type of target therapy can potentially benefit either in the front line or subsequent treatment settings.

The ability to provide personalized therapy based on molecular biology and the specifics of the individual patient's case, that's really gratifying. It's only the beginning with more novel agents in the horizon. In fact, more data on those agents and better understanding the biomarkers, can help us decide whether a patient has a condition that is sensitive or resistant to a certain panel of agents but also help us to really guide what's the best choice of a treatment for an individual case.

Lastly, I want to encourage people, both the providers and also patients, with their interest in contributing to T-cell lymphoma, to really participate in community outreach and participate in clinical trials.

Our knowledge is collective and the more that we participate in clinical trials, especially well-designed clinical study, the earlier that we get to the point where we would have those novel agents become available for patients.

I would highly encourage patients to go to dedicated centers with expertise for T-cell lymphoma diagnosis and treatment, and participate in well-designed trials in T-cell lymphoma space. We can do this together.