Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis.
OBJECTIVE
Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30(+) receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30(+) cutaneous T-cell lymphomas.


METHODS
Forty-eight patients with CD30(+) lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days.


RESULTS
Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sézary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (≥ 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy (n = 6), transaminitis (n = 1), and arthralgias and fatigue (n = 2).


CONCLUSIONS
Brentuximab vedotin is both active and well tolerated in cutaneous T-cell lymphoma and lymphomatoid papulosis, with an overall response rate of 73% and complete response rate of 35%.
All authors: The University of Texas MD Anderson Cancer Center, Houston, TX. mduvic@mdanderson.org.
Madeleine
M
Duvic
All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
Michael T
MT
Tetzlaff
All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
Pamela
P
Gangar
All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
Audra L
AL
Clos
All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
Dawen
D
Sui
All authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
Rakhshandra
R
Talpur
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D000079963:Brentuximab Vedotin; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D017730:Ki-1 Antigen / Q000032:analysis*; D054446:Lymphoma, Primary Cutaneous Anaplastic Large Cell / Q000188:drug therapy / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000276:immunology*; D017731:Lymphomatoid Papulosis / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012751:Sezary Syndrome / Q000188:drug therapy / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin