When used in combination and sequentially, available treatment options for mycosis fungoides (MF) and Sézary syndrome (SS) are now providing prolonged periods of progression-free survival (PFS), according to a prospective study following more than 2000 patients that included more than 500 with advanced-stage disease.

"The established skin- and blood-directed options can give durable control with the longest times to next systemic therapy in the range of 18 to 20 months," reported Abraham E. Bashir, MSc, MBBS, a dermatologist at University Hospitals Birmingham National Health Service, in the UK. 

Drawn from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study, a global observational registry created in 2015, the data presented by Bashir was focused on the 509 advanced-stage patients who have collectively received almost 2500 lines of therapy. PROCLIPI is collecting data on patients with cutaneous T-cell lymphomas across six continents.

No Accepted Standard Therapy for MF/SS 

So far, the advanced-stage MF and SS patients being followed in PROCLIPI have received a median of three lines of treatment. Currently, there is no accepted standard of care for these diseases, and one goal of PROCLIPI is to collect data to compare strategies in the real world, Bashir said in a presentation at the European Academy of Dermatology and Venereology (EADV) 2026 Congress in Vienna.

In these advanced stage patients, 70% have received systemic therapy first line. Almost all of the remaining have been treated with a skin-directed therapy. In 63% of those receiving a systemic therapy, two or more systemic therapies were combined In about two-thirds of the cases. With the remainder, systemic therapy was combined with a skin-directed treatment.

Whether used to treat stage IIB, stage IIIA, stage IIIB, or stage IVA, methotrexate, bexarotene, and interferon alpha were among the most common systemic therapies offered first line. For stage IIIa alone, acitretin was among the common systemic therapies.

The most common first-line skin-directed therapies for stage IIB, stage IIIA, stage IIIB, or stage IVA MF/SS included local radiation, electron beam therapy, extracorporeal photopheresis (ECP), and narrow-band ultraviolet B (NB-UVB) phototherapy.

In stage IVB disease, the CHOP regimen (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) was the most common first choice, but the top five choices — whether used alone or in combination — were filled out by radiation, ECP, interferon alpha, and NB-UVB phototherapy.

The highest rates of a complete plus a partial (CR + PR) response were achieved with gemcitabine (78%), romidepsin (60%), and brentuximab vedotin (60%). Bexarotene, ECP, and CHOP achieved CR + PR rates of approximately 50%, while methotrexate produced the lowest CR + PR rate at 29% of the commonly used agents even though it was the first-choice therapy for two of the stages (IIIa and IIIb).

On a ranked list of first-line therapies providing the longest time until initiation of a second-line agent, ECP led with a median time of 19.0 months. This was followed by brentuximab vedotin (10.3 months), interferon alpha (9.3 months), and bexarotene (8.8 months). Notably, methotrexate (5.0 months) and CHOP (2.9 months) were the last of the nine therapies on this list.

Relative to Monotherapy, Combinations Did Better 

When any combination regimen was compared to a monotherapy, there was an improved median time to next therapy. For example, when ECP monotherapy was compared to ECP in any combination, the median time to next therapy increased from 14.6 to 20.3 months. Similarly, gains were also seen in combinations compared with monotherapy for methotrexate (7.7 vs 4.8 months), interferon alpha (10.6 vs 5.2 months) and bexarotene (13.6 vs 6.3 months).

When second-line treatments were compared for a CR + PR response, the anti-CCR4 therapy mogamulizumab performed best (79%), followed by brentuximab vedotin (52%). In this setting ECP (38%), gemcitabine (38%), and interferon alpha (31%) did less well, but methotrexate (49%) was only slightly behind brentuximab.

However, the time to next therapy in the second-line setting was again longest for ECP (19.3 months) relative to any other second-line agent, including mogamulizumab (11.6 months), brentuximab vedotin (8.5 months), and gemcitabine (4.8 months). The time to next treatment was 10.7 months for second-line methotrexate and 10.3 months for second-line interferon alpha.

"Newer antibodies like mogamulizumab and brentuximab highlight an encouraging signal for a more targeted approach," Bashir said. But he acknowledged that more studies are needed to understand how these therapies are best sequenced with other options.

One message from these data is that dermatologists should continue to participate in the care of MF and SS even in advanced stages, he said. "Skin-directed care and dermatologist-led options, such as phototherapy and electron beam therapy, remain central and continue alongside systemic therapy across the whole disease course," Bashir said.

Presenting results of a retrospective 18-center Italian study of mogamulizumab at the 2026 EADV meeting, Gabriele Roccuzzo, MD, a researcher in the section of dermatology at the University of Turin, Italy, agreed that more data are needed to sequence therapies in MF and SS.

He also suggested on the basis of the Italian data that prognostic factors, particularly duration of response, might be helpful to clinicians for considering when to move from one second-line agent to another.

Four-Month ORR Predicts Better Outcomes 

This recommendation was based on his analysis of 93 MF/SS patients taking mogamulizumab, approved by the European Medicines Agency in 2018. In his study, an objective response rate persisting for at least 4 months (ORR4) was a predictor of sustained benefit.

Specifically, after a median 35 months of follow-up, the median 2-year overall survival (OS) was 72% but climbed to 76% among those meeting the ORR4 criterion. The 2-year OS was 60% (P =.006) among those who did not meet the criterion.

The same phenomenon was recorded for PFS, which was 52% overall, but increased to 58% of those who achieved ORR4 versus 35% (P = .001) among those who did not. This was further reflected in a shorter time to next treatment, for which the hazard ratio (HR) was three times higher (HR, 3.04; P =.003) for those not reaching ORR4 relative to those who did.

The Italian mogamulizumab study also associated skin rash with a greater likelihood of a robust clinical response to the monoclonal antibody, according to Roccuzzo.

Mogamulizumab was approved in many countries soon after the pivotal international, phase 3 MAVORIC trial showed a PFS benefit in the second-line setting, but Roccuzzo observed that the effort to standardize the use of this drug — like other MF/SS therapies — has been limited by the challenges of comparing strategies for a rare disease.

The EADV provides the bulk of funding for the PROCLIPI study, Bashir and Roccuzzo reported no potential conflicts of interest. 

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including dermatology and oncology, for several decades.