ASH 2024 | The current standard of care for CTCL

Yeah, so CTCL is a family of cutaneous lymphomas, primarily of T-cell origin, that are relatively rare in terms of new incidence, but in terms of prevalence affects tens of thousands of patients every year, many of which require therapy ongoing for most of their lives. So there’s a significant need for therapy. And the standard of care is based really on the breakdown of the disease at presentation. So many patients present, about two-thirds of the patients present with early stage disease, which means that the lymphoma is limited to a relatively small amount of the skin with no deep lesions and no involvement of any of the blood or lymph nodes. And about a third of the patients present with more advanced stage, with more systemic disease. 

For the patient with early stage, the standard of care initially is so-called skin-directed therapy which includes phototherapy, electromagnetic radiation, topical steroids, and so on. Many of these patients can go on for a fairly long time just rotating through these different skin-directed therapies. 

For the patients with advanced stage disease, those will need systemic therapy from the very beginning. However, a significant fraction, perhaps the majority of the patients with early stage disease as well eventually will need systemic therapy because they will stop responding to phototherapy or you know electron beam or topical therapy and therefore they’ll transition to having a need for systemic therapy even if they stay in a relatively early stage so they don’t have disease outside of the skin. 

The standard of care for skin-directed therapy hasn’t changed that much. Most therapies are quite effective for a duration of time. Perhaps the most significant change recently has been the use of low-dose total skin electron beam radiation which has made the total skin more feasible, more flexible, very often can be combined with other forms of therapy. There are also some new topical therapies that have been approved in the past five to eight years; nothing really very new recently.

In terms of systemic therapy, there are a number of drugs that were approved over the past 10 to 15 years, and for a long time, there was a lack of new drugs. Now, over the past five to six years, there have been a number of new drugs approved, and several more available in clinical trials that are close to being approved. The newest additions to the systemic therapy in cutaneous T-cell lymphoma are brentuximab vedotin, which is an anti-CD30 antibody-drug conjugate, which was approved based on a trial called ALCANZA, and is very effective particularly in CTCL that is expressing CD30, which is a surface marker, or in transformed MF, mycosis fungoides. Another systemic therapy was approved relatively recently is mogamulizumab, which is an antibody targeting CCR4, which is expressed in high density on the T-cells from CTCL patients. Those are the new drugs approved, there’s still a need for a number of additional new drugs, many of which are in trials, which we will discuss.

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