Background
Phase 3, open-label, international RCT. 128 patients with CD30-positive (≥10% expression) mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (pcALCL) who had received ≥1 prior systemic therapy. CD30 expression is present in ~40–50% of MF and nearly all pcALCL. Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate delivering the microtubule-disrupting payload monomethyl auristatin E (MMAE). Prior therapies included MTX, bexarotene, retinoids, and multiagent chemotherapy.
Interventions and follow up
Arm A: Brentuximab vedotin 1.8 mg/kg IV every 3 weeks (up to 16 cycles)
Arm B: Physician's choice — methotrexate 5–50 mg/wk orally OR bexarotene 300 mg/m²/day orally (investigator-selected at enrollment)
Primary endpoint: Objective global response lasting ≥4 months (ORR≥4mo)
Median follow up: 22.9 months
Arm B: Physician's choice — methotrexate 5–50 mg/wk orally OR bexarotene 300 mg/m²/day orally (investigator-selected at enrollment)
Primary endpoint: Objective global response lasting ≥4 months (ORR≥4mo)
Median follow up: 22.9 months
Results
ORR≥4 months: 56.3% vs 12.5%, RR 4.50, 95% CI 2.11–9.58, P<.0001
mPFS: 16.7 vs 3.5 months, HR 0.27, 95% CI 0.18–0.40, P<.0001
Complete response rate: 16% (BV) vs 1% (physician's choice)
ORR (any response): 67% vs 20%
MF subgroup — ORR≥4mo: 50% vs 10%
pcALCL subgroup — ORR≥4mo: 67% vs 20%
mPFS: 16.7 vs 3.5 months, HR 0.27, 95% CI 0.18–0.40, P<.0001
Complete response rate: 16% (BV) vs 1% (physician's choice)
ORR (any response): 67% vs 20%
MF subgroup — ORR≥4mo: 50% vs 10%
pcALCL subgroup — ORR≥4mo: 67% vs 20%
Adverse events
Overall (grade ≥3): 41% (BV) vs 47% (physician's choice); neutropenia grade ≥3 14%; infusion reactions 1%
Neurologic: Peripheral neuropathy any grade 67% vs 6%; grade ≥3 13% (BV). Peripheral neuropathy was dose-limiting but resolved or improved in 83% of affected patients following BV discontinuation
Neurologic: Peripheral neuropathy any grade 67% vs 6%; grade ≥3 13% (BV). Peripheral neuropathy was dose-limiting but resolved or improved in 83% of affected patients following BV discontinuation
Conclusions
Brentuximab vedotin significantly improved ORR≥4 months and PFS versus physician's choice in CD30+ MF and pcALCL, with a more than 4-fold improvement in the primary endpoint. These results established BV as a new standard of care for CD30-expressing cutaneous T-cell lymphoma and supported FDA approval in both MF and pcALCL indications.
Key Limitations
The CD30 ≥10% cutoff was selected on preclinical rationale; the optimal threshold for predicting benefit has not been definitively validated — exploratory analyses suggest benefit may extend across CD30 expression levels. Comparator arms (MTX or bexarotene) represent only a subset of available salvage therapies — no comparison to HDAC inhibitors (romidepsin, vorinostat) or mogamulizumab. Open-label design allows performance bias. The primary endpoint (ORR≥4mo) is a composite not uniformly used across CTCL trials, complicating cross-study comparison. Peripheral neuropathy is a clinically significant cumulative toxicity.
Clinical Context
Brentuximab vedotin received FDA approval (2017) for adult patients with primary cutaneous CD30-expressing T-cell lymphoma who have received prior systemic therapy, based on ALCANZA. CD30 testing (IHC) is now standard workup in CTCL. BV is particularly effective in pcALCL (near-universal CD30 expression) and in CD30-high MF. In CD30-lower MF, mogamulizumab (MAVORIC) — especially for Sézary syndrome — is a complementary option. ESMO lists BV among preferred options for CD30+ CTCL after prior systemic therapy.
References