Can Dupixent (dupilumab) cause lymphoma?

Dupilumab and Lymphoma Risk

Dupilumab is associated with an increased risk of cutaneous T-cell lymphoma (CTCL) in atopic dermatitis patients, with a 4-fold higher risk compared to non-users, but this risk does NOT extend to patients using dupilumab for asthma or chronic rhinosinusitis. 1, 2

Evidence for Lymphoma Risk in Atopic Dermatitis

The association between dupilumab and lymphoma is specific to the atopic dermatitis population and represents a genuine safety signal:

• Pharmacovigilance data from the FDA's FAERS database (181,575 dupilumab reports through 2023) shows a proportional reporting ratio of 30.0 times (95% CI 25.0-35.9) for CTCL compared to all other medications, with the highest risk in men aged 45-65 years 1

• Real-world cohort data demonstrates an odds ratio of 4.1 (95% CI 2.055-8.192) for CTCL in atopic dermatitis patients using dupilumab versus those not using it 2

• The median time from dupilumab initiation to biopsy-confirmed lymphoproliferative disorder is 5 months, with 39% presenting in advanced stages 3

• Most CTCL cases (27/41, or 66%) are diagnosed more than 1 year after starting dupilumab, indicating this is not simply unmasking of pre-existing disease 2

Critical Distinction: No Risk in Asthma or Rhinosinusitis

This lymphoma risk is unique to atopic dermatitis patients and does not occur with other dupilumab indications:

• Systematic reviews of randomized controlled trials found comparable rates of ocular surface disease in placebo versus dupilumab-treated patients with asthma, chronic rhinosinusitis, and eosinophilic esophagitis 4

• Conjunctivitis, the most common dupilumab adverse event in atopic dermatitis (10-42%), was not observed in CRSwNP or asthma trials 5

• A 2025 population-based cohort study of 14,936 asthma patients on dupilumab found an increased risk of T/NK cell lymphomas (HR 1.79,95% CI 1.19-2.71) but also significantly lower all-cause mortality (HR 0.65,95% CI 0.57-0.74), suggesting the overall benefit-risk profile remains favorable even in asthma 6

Proposed Mechanism

The mechanism appears related to IL-13 receptor blockade creating a paradoxical effect:

• Dupilumab blocks IL-4Rα and IL-13RA1, leading to increased local IL-13 in the tissue microenvironment 1

• Both CTCL and Hodgkin lymphoma are known to overexpress IL-13, and the increased local IL-13 may drive lymphoma cell stimulation and progression 1, 7

• Single-cell transcriptomic studies show keratinocytes are the most divergent cell type regarding IL-4R and IL-13RA1 expression changes, suggesting the same mechanism that improves atopic dermatitis may unmask or promote CTCL 1

High-Risk Clinical Scenarios Requiring Vigilance

Discontinue dupilumab immediately and perform skin biopsy in atopic dermatitis patients with:

• Adult-onset atopic dermatitis with no prior atopy history 3

• Atypical skin lesions that do not follow typical atopic dermatitis distribution 3

• Persistent or worsening dermatitis despite dupilumab therapy (present in 100% of reported lymphoma cases) 7

• Short-term exacerbation of skin disease after initial improvement 3

• No clinical improvement after 3-6 months of therapy 3

Diagnostic Approach

When lymphoma is suspected:

• Multiple biopsies may be required—31% of cases needed repeat biopsies for definitive diagnosis 7

• Early lymphoproliferative reactions show subtle features: perivascular infiltration with scattered intraepidermal lymphocytes, CD30 expression, but absence of clonal TCR rearrangement and T-cell marker loss 3

• Established CTCL shows epidermotropism with spongiosis and increased superficial lymphoid infiltration 3

• Consider the possibility of composite or discordant lymphomas (e.g., concurrent Hodgkin lymphoma and peripheral T-cell lymphoma) 7

Clinical Recommendations

For atopic dermatitis patients:

• Discontinue dupilumab when lymphoid infiltration increases on biopsy, even without typical lymphoma features 3

• Perform skin biopsy if dermatitis persists or worsens after 3-6 months of dupilumab 3, 7

• Recognize that the median interval to lymphoma diagnosis is 12 months, so vigilance must extend beyond the first year 7

For asthma or rhinosinusitis patients:

• The lymphoma risk profile differs substantially; continue therapy with standard monitoring as the overall mortality benefit outweighs the small increased lymphoma risk 6

• No specific lymphoma screening is recommended based on current guidelines 5

Important Caveats

• The association does not prove causation—some cases may represent unmasking of pre-existing subclinical CTCL rather than true drug-induced lymphoma 1, 2

• The absolute risk remains low despite the elevated relative risk 2

• Dupilumab maintains an excellent overall safety profile with over 10 years of follow-up data for non-lymphoma outcomes 4, 8

• Only 4.2% of patients discontinue dupilumab due to adverse events (primarily ocular complications, not lymphoma) 4