Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis

Madeleine Duvic, Michael T. Tetzlaff, Pamela Gangar, Audra L. Clos, Dawen Sui, Rakhshandra Talpur

Research output: Contribution to journalArticle

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Abstract

Purpose: 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 Patients and 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 overal 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) Conclusion: 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%

Original languageEnglish (US)
Pages (from-to)3759-3765
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number32
DOIs
StatePublished - Nov 10 2015
Externally publishedYes

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Lymphomatoid Papulosis
Cutaneous T-Cell Lymphoma
Mycosis Fungoides
cAC10-vcMMAE

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

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Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis. / Duvic, Madeleine; Tetzlaff, Michael T.; Gangar, Pamela; Clos, Audra L.; Sui, Dawen; Talpur, Rakhshandra.

In: Journal of Clinical Oncology, Vol. 33, No. 32, 10.11.2015, p. 3759-3765.

Research output: Contribution to journalArticle

Duvic, Madeleine ; Tetzlaff, Michael T. ; Gangar, Pamela ; Clos, Audra L. ; Sui, Dawen ; Talpur, Rakhshandra. / Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 32. pp. 3759-3765.
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abstract = "Purpose: 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 Patients and 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 overal 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/S{\'e}zary 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) Conclusion: 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{\%}",
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T1 - Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis

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AU - Tetzlaff, Michael T.

AU - Gangar, Pamela

AU - Clos, Audra L.

AU - Sui, Dawen

AU - Talpur, Rakhshandra

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N2 - Purpose: 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 Patients and 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 overal 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) Conclusion: 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%

AB - Purpose: 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 Patients and 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 overal 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) Conclusion: 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%

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