TY - JOUR
T1 - Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies
AU - Bartlett, Nancy L.
AU - Chen, Robert
AU - Fanale, Michelle A.
AU - Brice, Pauline
AU - Gopal, Ajay
AU - Smith, Scott E.
AU - Advani, Ranjana
AU - Matous, Jeffrey V.
AU - Ramchandren, Radhakrishnan
AU - Rosenblatt, Joseph D.
AU - Huebner, Dirk
AU - Levine, Pamela
AU - Grove, Laurie
AU - Forero-Torres, Andres
N1 - Funding Information:
This work was supported by Seattle Genetics, Inc. and Takeda Pharmaceuticals International Co. The authors would like to thank Dr. Eric Sievers for assistance in development of the manuscript as an employee of Seattle Genetics, Inc. The authors wish to acknowledge Jennifer R. Houser for providing medical writing services and Baiteng Zhao for pharmacokinetic support as employees of Seattle Genetics, Inc. RC is a K12 scholar supported by National Cancer Institute of the National Institutes of Health under award number K12CA001727. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
PY - 2014/3/19
Y1 - 2014/3/19
N2 - Background: Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Methods. Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. Results: The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. Discussion. With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Conclusions: Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. Trial registration. United States registry and results database ClinicalTrials.gov NCT00947856.
AB - Background: Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Methods. Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. Results: The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. Discussion. With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Conclusions: Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. Trial registration. United States registry and results database ClinicalTrials.gov NCT00947856.
KW - Brentuximab vedotin
KW - Hodgkin lymphoma
KW - Relapse
KW - Retreatment
KW - Systemic anaplastic large cell lymphoma
UR - http://www.scopus.com/inward/record.url?scp=84899128074&partnerID=8YFLogxK
U2 - 10.1186/1756-8722-7-24
DO - 10.1186/1756-8722-7-24
M3 - Article
C2 - 24642247
AN - SCOPUS:84899128074
SN - 1756-8722
VL - 7
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
IS - 1
M1 - 24
ER -