Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma

Anas Younes, Ajay K. Gopal, Scott E. Smith, Stephen M. Ansell, Joseph D Rosenblatt, Kerry J. Savage, Radhakrishnan Ramchandren, Nancy L. Bartlett, Bruce D. Cheson, Sven De Vos, Andres Forero-Torres, Craig Moskowitz, Joseph M. Connors, Andreas Engert, Emily K. Larsen, Dana A. Kennedy, Eric L. Sievers, Robert Chen

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Abstract

Purpose: Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas. Patients and Methods: In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility. Results: The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. Conclusion: The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy.

Original languageEnglish
Pages (from-to)2183-2189
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number18
DOIs
StatePublished - Jun 20 2012

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Hodgkin Disease
Stem Cell Transplantation
cAC10-vcMMAE
Safety
Antibodies
Peripheral Nervous System Diseases
Secondary Prevention
Neutropenia
Intravenous Infusions
Radiology
Pharmaceutical Preparations
Nausea
Disease-Free Survival
Fatigue
Disease Progression
Diarrhea
Lymphoma
Observation
Pathology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. / Younes, Anas; Gopal, Ajay K.; Smith, Scott E.; Ansell, Stephen M.; Rosenblatt, Joseph D; Savage, Kerry J.; Ramchandren, Radhakrishnan; Bartlett, Nancy L.; Cheson, Bruce D.; De Vos, Sven; Forero-Torres, Andres; Moskowitz, Craig; Connors, Joseph M.; Engert, Andreas; Larsen, Emily K.; Kennedy, Dana A.; Sievers, Eric L.; Chen, Robert.

In: Journal of Clinical Oncology, Vol. 30, No. 18, 20.06.2012, p. 2183-2189.

Research output: Contribution to journalArticle

Younes, A, Gopal, AK, Smith, SE, Ansell, SM, Rosenblatt, JD, Savage, KJ, Ramchandren, R, Bartlett, NL, Cheson, BD, De Vos, S, Forero-Torres, A, Moskowitz, C, Connors, JM, Engert, A, Larsen, EK, Kennedy, DA, Sievers, EL & Chen, R 2012, 'Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma', Journal of Clinical Oncology, vol. 30, no. 18, pp. 2183-2189. https://doi.org/10.1200/JCO.2011.38.0410
Younes, Anas ; Gopal, Ajay K. ; Smith, Scott E. ; Ansell, Stephen M. ; Rosenblatt, Joseph D ; Savage, Kerry J. ; Ramchandren, Radhakrishnan ; Bartlett, Nancy L. ; Cheson, Bruce D. ; De Vos, Sven ; Forero-Torres, Andres ; Moskowitz, Craig ; Connors, Joseph M. ; Engert, Andreas ; Larsen, Emily K. ; Kennedy, Dana A. ; Sievers, Eric L. ; Chen, Robert. / Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 18. pp. 2183-2189.
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AU - Ansell, Stephen M.

AU - Rosenblatt, Joseph D

AU - Savage, Kerry J.

AU - Ramchandren, Radhakrishnan

AU - Bartlett, Nancy L.

AU - Cheson, Bruce D.

AU - De Vos, Sven

AU - Forero-Torres, Andres

AU - Moskowitz, Craig

AU - Connors, Joseph M.

AU - Engert, Andreas

AU - Larsen, Emily K.

AU - Kennedy, Dana A.

AU - Sievers, Eric L.

AU - Chen, Robert

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N2 - Purpose: Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas. Patients and Methods: In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility. Results: The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. Conclusion: The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy.

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