10 Experts Predict the Future of CTCL Treatment

Progression may feel slower in rare disease fields such as cutaneous T-cell lymphoma (CTCL) —the dearth of patients mean fewer data to inform clinical investigation, which means a more stagnant pipeline.

But many experts would argue the progression is more deliberate than it is slow. In fact, what prescribing clinicians may be able to achieve in CTCL in the coming years may have been clearly mapped out for just as long.

During the 6th World Congress of Cutaneous Lymphoma (WCCL) in Montreal, QC this month, OncLive asked its expert interview guests a recurring question: “What is a belief about treating CTCL that you think the field will abandon in the next decade?”

Watch the video above or read the transcripts below to hear what 10 world-leading experts in CTCL had to say about what to anticipate from the rare cancer field by 2036.

Jan P. Nicolay, MD, PhD: I think what we definitely will abandon is monotherapy. We now have so much evidence that combination and even upfront direct first-line combination is superior to monotherapy. Therefore, the future will belong to the combination therapies, even in a first-line setting.

Watch more: Dr Nicolay on Biomarkers and Mechanisms to Support Mogamulizumab

Gabriele Roccuzzo, MD: I think that we will move from a stage-based approach of the treatment to a better way to stratify our patients — combining some clinical and histological features that are not currently in the TNMB staging. So, I think we're moving from that kind of approach, and probably in 5-10 years, we will have better prognostic information on these patients.

Marie Beylot-Barry, MD, PhD: I think we will no longer [provide] chemotherapy or non-specific therapy. We will focus on more specific therapies with targeted antibodies, and I think the main point is to select the best treatment for the best patients, and we need biomarkers. With the new technologies that we have, we can select, perhaps in the future, good patient for the good treatments.

Watch more: Dr Beylot-Barry on Patient Selection, Follow-up of Moga-Stop in Sézary Syndrome

H. Miles Prince, MD, MBBS: In terms of what is going to be used less and less, I think chemotherapy is definitely going to be used less. There's still certain situations where chemotherapy is required, and those are when patients fit into the very high-risk group — with nodal disease with large cell transformation. And we still don't know if that's the right thing to do, and that's the big question: when do we use chemotherapy? And in 10 years' time, I would like to see no chemotherapy being used for cutaneous T cell lymphoma at all.

Watch more: Dr Prince on the Design of the Comparison of MAVORIC and Real-World Vorinostat

Lena Specht, MD, DMSc: We are going to see more and better targeted therapies, and I think that the we will also see combinations with radiation therapy and some of these particular immunomodulatory treatments. Radiation therapy has in itself immunomodulatory effects, and I think we'll get more research results elucidating these mechanisms and making it possible for us to combine them in a rational fashion — and thereby hopefully greatly improve the outcome for our patients.

Watch more: Dr Specht on the Significance of Data for Mogamulizumab vs SOC in Denmark for Patients With MF/SS

Neha Mehta-Shah, MD, MSCI: I think that there has been a pattern of really focusing only on overall response rate, and I'm hoping over the time of my career that people will really look at quality of life as an endpoint for clinical trials. I think us and many others are working on tools that really represent the quality-of-life experience for patients with this disease, and I think we've made a lot of headway in developing tools like that that are really specific for this disease, and over time I would hope and believe that will become an important surrogate endpoint that will lead to information about how we should use one drug over another in sequencing of therapy.

Watch more: Dr Mehta-Shah on the Future of CTCL Novel Drug Development

Julia Dai, MD: I think historically the treatments have been focused on previous chemotherapies or pulling things from other diseases that have been more in the realm of cytotoxicity. And I think now we're all learning that immuno-enhancing or immuno-activating may be the key for us. We've already seen people move away from conventional chemotherapies and towards biological or immunotherapies, and I think we're only doing that more so. We're really not seeing any data from toxic treatments, we're really seeing a lot more biologic treatments that are thought to be helpful, longer acting. I think we've already seen that trend, and I think we're only going to see more of that.

And that's similar to what we're trying to learn from tofacitinib — the other JAK inhibitors, those are more biologically active rather than toxic. That's not necessarily novel, but just another layer I think that we're going to continue adding on in the future of therapies for this disease.

Oleg Akilov, MD, PhD: Some treatments do come back — whatever we don't like today may take a different shape and return. You know, fenretinide is a good example, right? We were looking at an IV retinoid for quite some time, and it came, didn't stay, and came back. But there are a lot of interesting topics we kind of don't touch. Genomic instability is a cornerstone of this disease — how do you stabilize the chromosomes in aging lymphocytes? That's the million-dollar question, but it almost feels like a question of the fountain of youth: how do you preserve life when it starts falling apart?

I think this is a huge problem in our field, because we like pushing the boundaries — instead of just eliminating cancer cells, we're trying to fortify the body. And it's already so far beyond oncology, because there's a reason all our patients are 63-plus. We have some young patients, but the majority are elderly, because this is a disease of aging cells. That's the problem — one nobody has quite approached yet, and I think that's where the field is going to go.

Stefan Barta, MD, MS: We can say the same thing for cutaneous T-cell lymphoma that I think we're moving to in all other cancers: that we're moving away from the cytotoxic chemotherapy and to more targeted therapies andimmunotherapies. And I think we've seen a revolution in oncology. I understand we've only been able to use multi-agent combination therapy since the 1960s and 1970s, and that was a big revolution at the time, but I think now we're having another revolution of immunotherapies.

I'm very excited to see more cellular therapies, and we're in the infancy of CAR-T cell therapy, and there were a lot of obstacles to overcome to even get that started, but there's a lot of momentum now, and I'm hopeful that we will find targets and that we will find cure to a disease. When I'm teaching students or fellows, I still have to say 'It's a mostly incurable disease, other than with transplant.' I hope I don't have to say that much longer.

And that is the interesting part — with some of the immunotherapeutic options, we have seen some what we would call long-term survivors who might actually have been cured, for example, with extracorporeal photophoresis or with checkpoint inhibitors. I think all of us have some patients who underwent the treatment and the lymphoma never came back. So, that just provides a glimmer of hope that this is the direction to go. I'm very, very optimistic that we can see that still in my lifetime.

Christiane Querfeld, MD, PhD: We will really move forward towards treating more the tumor cells plus the tumor environment. Chemotherapy will be probably less and less you utilized, so then we can focus on those drugs that really work effectively without harming patients. I mean, you don't want to purposely harm patients, but chemo drugs have more side effects, right? That's no question. And still, it's important to have it in case patients need something for rapidly progressing [CTCL]. But ultimately we want to start early in our treatment that actually will treat the tumor and the environment so effectively that we then have to go to the next point.

So, I think the trend is to have treatments that are better tolerated. There are treatments that are really targeting more specific things — really knowing details, mechanistic-based. And I think that's where other cancers go too, and I think in cutaneous lymphoma we have been always ahead of everyone because we can study it so easily with skin biopsies.

Watch more: Dr Querfeld on Sequencing Strategies for Mogamulizumab