Tofacitinib 2% Cream Yields Responses and Is Safe in Mycosis Fungoides

The use of tofacitinib 2% cream led to encouraging response rates and a favorable safety profile in patients with early-stage mycosis fungoides, according to findings from a pilot study that were presented at the 2026 World Congress of Cutaneous Lymphomas.¹

At the data cutoff date, a total of 10 patients received treatment with tofacitinib 2% cream, and 7 patients had data available for primary end point analysis after completing 12 weeks of treatment. Of these 7 evaluable patients, 3 achieved a partial response (PR) at 12 weeks, defined as a 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline to after 12 weeks of therapy.

“For many of us, the question is no longer whether JAK inhibition will be effective in cutaneous lymphoma, but how to best deliver it safely for durable responses for our patients,” Julia Dai, MD, said in the presentation. “Topical therapy may be one of those opportunities.”

Dai is an assistant professor of dermatology at McGovern Medical School at UT Health; as well as an assistant professor of dermatology and the dermatology residency program director at The University of Texas MD Anderson Cancer Center in Houston.

What was the rationale for investigating topical tofacitinib in mycosis fungoides?

Dai explained that preclinical studies have shown that the deregulation of JAK/STAT signaling is associated with mycosis fungoides pathogenesis. In particular, STAT5 activation through JAK1 and JAK3 plays a role in the development of early-stage mycosis fungoides.² Tofacitinib is a selective JAK1 and JAK3 inhibitor that the present study investigators selected for investigation to determine its potential in blocking the STAT5 activation pathway.¹

“Preclinical data…from our group did show that early-stage patients…may be more responsive to tofacitinib,” Dai added.

What was the design of this pilot study of tofacitinib 2% cream in patients with mycosis fungoides?

This single-center study enrolled patients with stage IA to IIA mycosis fungoides. Patients applied tofacitinib 2% cream 2 times per day to a maximum of 5 mycosis fungoides index lesions. Patients had the option to extend treatment to a maximum of 1 year.

Index lesion response rate (defined as at least a 50% improvement in mCAILS score) from baseline to after 12 weeks of therapy served as the primary end point. Investigators also collected paired skin biopsies at week 0 and week 4 for use in exploratory correlative studies.

What is important to note about the patient population enrolled in the pilot study of tofacitinib 2% cream in patients with mycosis fungoides?

The patients had a median age of 70 years, and most were White, had Stage IA disease, and had classic patch plaque phenotypes. Additionally, 2 patients had a follicular tropic genotype.

Seven patients are ongoing in the study, and 3 additional patients have withdrawn from the study due to either lack of response or logistical issues.

During the presentation, Dai highlighted 2 cases of interest. The first patient was a 61-year-old male patient with folliculotropic mycosis fungoides involving the face. This patient had previously experienced limited benefit with topical steroids, but there was also concern for steroid-induced atrophy.

“His case nicely illustrates a potential therapeutic option for patients with facial involvement, a case where treatment options oftentimes are limited due to toxicity,” Dai noted. “Time will tell if other [patients with] folliculotropic [disease] will also respond. We do sometimes see superficial topical therapies [elicit] some response in folliculotropic cases, but [they are] not as robust.”

The second case involved a 78-year-old female patient with classic patch black mycosis fungoides who had experienced refractory disease for decades. This patient had not responded to previous treatment with mechlorethamine (topical nitrogen mustard). In the present study, although this patient did not achieve a clinical PR at week 12, she still had substantial benefit and decided to remain on the study, despite experiencing logistical challenges related to traveling to receive treatment.

“[This was] a nice case that highlights that the real-world [effect] of response from a patient perspective may sometimes be disordered,” Dai added.

What was the safety profile of tofacitinib 2% cream in patients with mycosis fungoides in this pilot study?

The investigators deemed tofacitinib 2% cream to be well tolerated. One patient experienced grade 1 skin irritation that resolved after pausing treatment. No patients reported serious or severe adverse effects. Across the total patient population, there was an approximate 1.6-point reduction in the pruritus visual analog scale.

What are the next steps for this pilot study evaluating tofacitinib 2% cream in patients with mycosis fungoides?

The findings seen so far in this pilot study support ongoing enrollment to this study, which has an enrollment goal of 20 patients. The study will continue to define the efficacy of tofacitinib 2% cream in patients with early-stage mycosis fungoides.

“This is an interim analysis,” Dai concluded. “We hope to continue study accrual. Importantly, we are excited to integrate correlative studies, which we find will be helpful in understanding the biologic basis for response and resistance. We don’t know what these patients expressed in terms of genomics. I hope [we] will present [those data in 2027].”

References

1. Dai J, Ni X, Torres-Cabala C, Huen A. A pilot study to assess safety and efficacy of tofacitinib 2% cream in the treatment of early-stage mycosis fungoides. Presented at: 2026 World Congress of Cutaneous Lymphoma. June 25-27, 2026. Montreal, Canada. Abstract 1B.02.
2. Kashyap A, Dai J, Ni X. Therapeutic targeting of the janus kinase/signal transducer and activator of transcription pathway in cutaneous T-cell lymphoma. Cancers (Basel). 2025;17(4):568. doi:10.3390/cancers17040568