Management of Mogamulizumab-Associated Rash Represents Key Focus in R/R CTCL Care

For patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL) receiving treatment with mogamulizumab-kpkc (Poteligeo), distinguishing mogamulizumab-associated rash from disease progression, according to Brad Haverkos, MD, who added that managing this adverse effect (AE) is crucial to ensure treatment benefit.

In an interview with OncLive®, Haverkos dived into his approaches for CTCL treatment-selection and management in clinical practice. Haverkos specifically spotlighted mogamulizumab and subsets of patients who may benefit most from the agent, along with notable considerations for the identification and management of mogamulizumab-associated rashes.

Haverkos is an associate professor of medicine and hematology at the University of Colorado Anschutz in Aurora, Colorado.

OncLive: How do you approach treatment for patients with CTCL following initial diagnosis?

Haverkos: Usually, CTCL is approached with a stage-based [strategy]. The first step in figuring out the best treatment is to stage the patient appropriately by looking at their skin and getting an assessment of their skin burden of disease, and then assessing if they have lymph node involvement, perhaps visceral involvement, which is exceptionally rare, or blood involvement. These factors really help us decide how best to treat [each] patient. Based on that composite score, you get a stage. The vast majority of patients who present with early-stage disease have skin-only involvement. Skin-only, early-stage patients, especially those who would be classified with a patch-stage disease that has very flat lesions, have an excellent prognosis.

[Patients with patch-stage CTCL have] excellent outcomes in general and for the most part, live a normal life expectancy. However, their disease is generally bothersome to them and affects their quality of life. We generally approach those early-stage patients with a skin-directed approach—typically narrow band UVB light therapy or phototherapy is our mainstay therapy.

For the patients that present with more advanced-stage disease, [which] most people would classify as having these lesions that we call tumors, having blood involvement, or having lymph node or organ involvement, which again, is exceptionally rare. [Patients with advanced-stage CTCL] are approached differently, usually with systemic therapy with or without some skin adjunct therapy.

What are the common signs of progression that you look for in patients with CTCL?

Patients who typically present with early-stage disease, we often treat them with narrowband UVB light or phototherapy. A portion of [early-stage patients] will progress and need systemic therapies or progress and be recalcitrant to skin-directed therapies. Once we kind of define [early-stage patients] as recalcitrant to having skin-directed therapy, we think about moving on to systemic therapies. [Additionally,] if they have an inadequate response to skin-directed therapy, we add some sort of adjunct from a systemic therapy. Typically, if patients just have skin-only disease, it would still be classified as early-stage disease defined as either patches or plaques. We often treat [patients with skin-only disease] with a drug called bexarotene [Targretin].

Sometimes we think about adding other drugs, like interferons. The old formulation of interferon, peginterferon alfa-2a [Pegasys] is no longer available; we now more often use a drug called ropeginterferon alfa-2b-njft [Besremi]. Those are some kind of things that we think about early on for patients with skin-only disease.

When you move to more advanced-stage disease, such as patients with tumor involvement that has more raised lesions or ulcerative plaque–like lesions, we think about some of our arguably more effective or potent systemic therapies. [For example,] HDAC inhibitors like romidepsin [Istodax] or pralatrexate are certainly drugs that we often think about in [the advanced-stage space].

[Advanced-stage treatment] is a nuanced approach that takes into account a number of different factors, not just the stage, but also the logistics, comorbidities, and other factors that are at play. One of the other factors that influence our choice of systemic therapy is blood involvement. Other histologic features that can be a factor [for advanced-stage treatment] is something called large-cell transformation. Also, if [patients are] CD30-positive, that may influence our decision to use a drug like brentuximab vedotin [Adcetris].

For patients with blood involvement, we really tend to think about mogamulizumab. We've learned over the years that different drugs respond in different compartments or different disease settings better [than others]. [This understanding] has allowed us to approach patients in a much more individualized [manner]. [For example,] some of the histologic features [of patients] may influence a decision to go one direction; for example, if they have blood involvement, then we tend to steer toward a drug like mogamulizumab.

There are different degrees of blood involvement, and certainly if [patients] have a low burden of blood involvement, we still think about things like photopheresis, interferons, and bexarotene, or potentially all 3 as good options for these patients. For patients with higher degrees of blood burden, ones that we classify as B2-disease or Sezary syndrome, the National Comprehensive Cancer Network and others recommend mogamulizumab as the go-to option, and that's certainly my approach as well.

What has been your experience with mogamulizumab and managing AEs in clinical practice?

In general, [mogamulizumab] a well-tolerated therapy. I have patients in their 90s who get [mogamulizumab] and do very well on the drug, with very minimal AEs. The most common AEs that we see are relatively mild things like fatigue, rare infusion reactions, and some headaches.

The AE that is most challenging is the rash that can ensue from mogamulizumab itself. It is tough in a disease that presents as a rash to have a drug that also causes rash. Frankly, many of the drugs that we use often do bring out some degree of rash, at least early on in therapy. [Therefore,] we often try to push through therapy when they have that kind of rash in the early onset.

In terms of response, responses in CTCL vary based on compartment response. If you were to look at the phase 3 MAVORIC study [NCT01728805], which compared mogamulizumab with vorinostat [Zolinza], while using pretty tight criteria to define response, responses with mogamulizumab were appoximately 30%.^1,2 However, if you look and break it down by compartment response and look at patients with blood response vs skin response vs lymph node response, you see high responses in the blood, right around 70% vs approximately 40% in the skin and approximately 20% in lymph nodes.

We also see the time to response is better in blood [with mogamulizumab]. These [data] demonstrate that mogamulizumab is most effective in patients with blood involvement. We see very early quick responses in the blood within weeks to months, and it takes longer for that skin response to happen—around 3 months is the median time to response in skin. For patients with Sezary syndrome, [mogamulizumab is] really our go-to drug. We often will see very high responses in the blood, and then the skin, if we stick with it, will eventually tend to get better [too].

[Mogamulizumab] is not a drug that we tend to think about in patients with lymph node or organ involvement, or in patients with large-cell transformation who were excluded from MAVORIC. In some of these populations and challenging [histologies], there is growing data thinking about using mogamulizumab in combination with other therapies.

Combination regimens are a theme all throughout CTCL, not just with mogamulizumab. We often think about combining therapies because of the mixed responses that we get in blood vs skin vs lymph nodes. We're still studying and learning how best to combine mogamulizumab, but a number of ongoing studies are looking at combinations, with some published data showing that maybe the duration of response is a little bit longer in those patients, which certainly makes sense with what we see clinically.

How do you manage rashes associated with mogamulizumab? How do you work alongside dermatologists in clinical practice?

Mogamulizumab-associated rash is super challenging to deal with and is a common issue that we run into. The rash can happen early, it can happen later after many months of therapy, and it can present as a whole host of different clinical manifestations. [Mogamulizumab-associated rashes] can look almost identical to CTCL. On clinical grounds alone, it's really impossible to distinguish a rash from progression of disease. We often will get skin biopsies to try to [distinguish mogamulizumab-associated rashes and disease progression]. Granted, even with a skin biopsy, it sometimes can be very challenging to decipher what is mogamulizumab rash vs what is progression. However, a skin biopsy is our best tool to help us understand the etiology of the rash.

In terms of treatment of mogamulizumab rash, there are a lot of different opinions out there, and there are lots of different approaches. Certainly, none of us know the absolute right way to approach [mogamulizumab rash]. Some studies suggest that patients who have a rash actually are ones that respond better. We really try not to make [rashes] a dose-limiting toxicity, and if there's a way to treat through them, we certainly try to do that. In my clinic, we've utilized steroids to treat rashes or things like oral methotrexate. There are other approaches as well that people are utilizing besides prednisone and methotrexate, and we'll learn more as time goes on.

What are the next steps for mogamulizumab in the CTCL treatment paradigm?

What I'm most excited about and look forward to in the years ahead is being able to have combination studies, with safe, well-tolerated combination therapies that can get quicker responses in the skin. Patients come in with complaints of pruritus, itching, and skin lesions. Often, most of our drugs take 3 months to work in the skin. [Therefore,] one of our goals moving forward is to find ways to get faster relief to our patients and improvement in their symptom burden and skin lesions. My suspicion is that's going to come by some combination therapies and perhaps additional targeted therapies, which is something else that I'm looking forward to in the years ahead.

References

1. Kim Y, Bagot M, Zinzani P, et al. Safety of mogamulizumab in mycosis fungoides and sézary syndrome: final results from the phase 3 MAVORIC study. Blood. 2019;134(suppl 1):5300. doi:10.1182/blood-2019-122778
2. Study of KW-0761 versus vorinostat in relapsed/​refractory CTCL. ClinicalTrials.gov. Updated April 25, 2025. Accessed May 19, 2026. https://clinicaltrials.gov/study/NCT01728805