Cutaneous T‐cell lymphoma following dupilumab use: a systematic review

Abstract

In recent years, studies have associated dupilumab with unmasking or progression of cutaneous T‐cell lymphoma (CTCL). The objective of this study was to synthesize reported cases of CTCL in the setting of dupilumab use. Two independent reviewers conducted a systematic review using PubMed and Embase databases. Twelve studies, of 27 total patients, were included. Dupilumab‐associated CTCL was diagnosed on average 7.8 months following dupilumab initiation. Of reports that included body surface area (BSA), 100% had a BSA >50% prior to diagnosis, and the majority of patients were diagnosed at later stages of disease: stage III (4/18) or IV (6/18). Post‐dupilumab biopsies revealed a greater density of cells and a predominant lichenoid pattern, compared to various histologic patterns and less cell density in pre‐dupilumab biopsies. The majority of TCR gene rearrangement studies were equivocal (20%) or negative (60%), posing a potential diagnostic pitfall. Limitations included lack of standardized data collection and reporting and a small number of studies. We suggest that earlier biopsies, three to four months after initiation of dupilumab, may be helpful for earlier recognition of CTCL in patients who are not improving, progressing, or have morphologic changes on dupilumab.

Angioimmunoblastic T-cell lymphoma unmasked by treatment with dupilumab

“…Most patients presenting with CTCL triggered by dupilumab are diagnosed with more advanced disease and it is thought that dupilumab causes rapid worsening in CTCL via immune dysregulation with a Th2-dominant immune profile. 5 To our knowledge, AITL occurring in the setting of dupilumab therapy has not been previously reported. Notably, AITL is a significantly more aggressive disease compared to CTCL.…”

“…The overall 5-year survival rate of AITL is 33% whereas 5-year survival for mycosis fungoides is 88%. 1 , 5 …”

Dupilumab-Associated Mycosis Fungoides with a CD8+ Immunophenotype

“…To date, 12 studies including a total of 27 patients report the development of CTCL after dupilumab treatment for an initial diagnosis other than CTCL, or demonstrate exacerbation of CTCL with dupilumab [ 14 ]. Our case demonstrates such a conundrum, where several outside biopsies were performed showing spongiotic and lichenoid patterns.…”

“…For a complete review of demographic and histologic findings of recently reported dupilumab-associated CTCL cases, please refer to the systematic review [ 14 ].…”

“…Several case studies in recent years have associated unmasking or progression of cutaneous T-cell lymphomas (CTCL) with dupilumab treatment [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. To date, all cases that have reported a CD4:CD8 ratio have shown a greater proportion of CD4+ cells [ 14 ]. Here we highlight a case of dupilumab-associated mycosis fungoides (MF) with a CD8+ predominant immunophenotype.…”