Can brentuximab vedotin be used in a patient with cutaneous T‑cell lymphoma whose tumor expresses CD30 in only 5% of cells?

Brentuximab Vedotin in Low CD30-Expressing Cutaneous T-Cell Lymphoma

Brentuximab vedotin can be used in cutaneous T-cell lymphoma with only 5% CD30 expression, as clinical responses have been documented at all levels of CD30 positivity, including very low expression. 1

Evidence Supporting Use at Low CD30 Expression

The most recent NCCN guidelines (2022) explicitly state that "interpretation of CD30 expression is not universally standardized, and responses with brentuximab vedotin have been observed at all levels of CD30 expression, including in patients with very low or absent CD30 expression." 1 This represents the strongest guideline-level evidence supporting treatment regardless of CD30 percentage.

Clinical Trial Data on Low CD30 Expression

In mycosis fungoides/Sézary syndrome patients, response rates were similar across CD30 expression levels:

• Patients with <10% CD30 expression: 50% overall response rate (5 of 10 patients) 2
• Patients with 10-50% CD30 expression: 58% overall response rate (7 of 12 patients) 2
• Patients with ≥50% CD30 expression: 50% overall response rate (3 of 6 patients) 2

The British Association of Dermatologists guidelines (2019) note that "those with <5% CD30 expression had a lower likelihood of global response than did those with CD30 expression ≥5%," but this does not preclude treatment—it simply indicates a somewhat reduced response probability. 1

FDA-Approved Indication

The FDA label for the ALCANZA trial (Study 4) included patients with CD30 expression ≥10% in at least one biopsy as the primary cohort. 3 However, supportive trials demonstrated that among 35 patients with 1-9% CD30 expression, 31% (11/35) achieved an objective response lasting at least 4 months. 3

Treatment Algorithm for Your Patient

For a patient with 5% CD30 expression:

1. Confirm the diagnosis with multiple biopsies from different lesions, as CD30 expression can be heterogeneous 1

2. Consider brentuximab vedotin if:

   • The patient has failed at least one prior systemic therapy 3
   • The disease is advanced (stage IIB or higher) or refractory 1
   • Alternative treatments have been exhausted or are inappropriate 1

3. Standard dosing: 1.8 mg/kg intravenously every 21 days for up to 16 cycles 1, 3

4. Monitor for response at 12 weeks (median time to response) 2

5. Expect peripheral neuropathy in approximately 57-65% of patients, mostly grade 1-2, which typically resolves after treatment completion 2, 4

Critical Caveats

The lower the CD30 expression, the lower the response rate, but responses still occur. 1 Your patient with 5% expression falls into a gray zone where the British guidelines suggest reduced likelihood of response compared to ≥5% expression, but the NCCN guidelines and clinical trial data show that responses can occur even with minimal or absent CD30 expression. 1, 2

Peripheral neuropathy is dose-limiting: If grade 2 neuropathy develops, dose reduction to 1.2 mg/kg should be implemented. 2 This occurred in 6 patients in the pivotal trial and allowed continued treatment. 2

Antigen loss can occur: CD30 expression may decrease with treatment, so if the patient progresses or recurs, repeat biopsy is essential to reassess CD30 status. 5

Real-world data supports efficacy: The Spanish Primary Cutaneous Lymphoma Registry reported a 67% overall response rate in 67 patients treated with brentuximab vedotin, with median progression-free survival of 10.3 months. 4 This included patients across the CD30 expression spectrum. 4