scholarly journals CYP3A-Mediated Drug-Drug Interaction Potential and Excretion of Brentuximab Vedotin, an Antibody−Drug Conjugate, in Patients With CD30-Positive Hematologic Malignancies

2013 ◽  
Vol 53 (8) ◽  
pp. 866-877 ◽  
Author(s):  
Tae H. Han ◽  
Ajay K. Gopal ◽  
Radhakrishnan Ramchandren ◽  
Andre Goy ◽  
Robert Chen ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Interaction Potential ◽  
Hematologic Malignancies ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Drug Drug Interaction ◽  
Antibody Drug

Panuveitis induced by brentuximab vedotin: a possible novel adverse event of an antibody-drug conjugate

2021 ◽  
pp. 1-4
Author(s):  
Philippos Apolinario Costa ◽  
Andrea Patricia Espejo-Freire ◽  
Kenneth Chen Fan ◽  
Thomas Arno Albini ◽  
Georgios Pongas
Keyword(s):  
Adverse Event ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

scholarly journals Successful rapid desensitization to the antibody–drug conjugate brentuximab vedotin in a patient with refractory Hodgkin lymphoma

2015 ◽  
Vol 22 (1) ◽  
pp. 188-192 ◽  
Author(s):  
Marie Fizesan ◽  
Christopher Boin ◽  
Olivier Aujoulat ◽  
Georges Newinger ◽  
Dana Ghergus ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Refractory Hodgkin Lymphoma ◽  
Antibody Drug

The Antibody-Drug Conjugate Brentuximab Vedotin (SGN-35) Induced Multiple Objective Responses in Patients with Relapsed or Refractory CD30-Positive Lymphomas in a Phase 1 Weekly Dosing Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2731-2731 ◽  
Author(s):  
Michelle Fanale ◽  
Nancy L Bartlett ◽  
Andres Forero-Torres ◽  
Joseph Rosenblatt ◽  
Sandra J Horning ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Objective Response ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Antibody Drug Conjugate ◽  
Phase 1 Study ◽  
Drug Conjugate ◽  
Antibody Drug

Abstract Abstract 2731 Poster Board II-707 Background: The antibody-drug conjugate (ADC) brentuximab vedotin (SGN-35) delivers the antitubulin agent monomethyl auristatin E (MMAE) to CD30-positive malignant cells by binding specifically to CD30 on the cell surface and releasing MMAE inside the cell via lysosomal degradation. In a previous phase 1 study with every 3 week dosing, 54% of patients achieved an objective response (CR/PR) at brentuximab vedotin doses ≥1.2 mg/kg [ASH 2008 abstract 1006]. Methods: To investigate the tolerability and antitumor activity of a more frequent dosing regimen, a multicenter phase 1 study was conducted in patients with refractory or recurrent CD30-positive lymphomas using a 3 + 3 dose-escalation design. Brentuximab vedotin was administered weekly for 3 weeks in 28-day treatment cycles at doses of 0.4 to 1.4 mg/kg (30-min or 2-hr IV infusions). Patients with stable disease or better (Cheson 2007) after two cycles were eligible to receive additional brentuximab vedotin treatment cycles. Results: A total of 37 patients, 31 with Hodgkin lymphoma (HL), 5 with systemic anaplastic large cell lymphoma (ALCL), and 1 with peripheral T-cell lymphoma, were enrolled and treated. Median age was 35 (range 13–82) and most patients (89%) had an ECOG performance status of 0/1. Patients received a median of 3 prior chemotherapy regimens (range 1–8); 62% previously received an autologous stem cell transplant. More than 50% of patients (21 of 37) had disease that did not respond to their most recent prior therapy. Dose-limiting toxicities included G3 diarrhea, G3 vomiting, and G4 hyperglycemia. The maximum tolerated dose was exceeded at 1.4 mg/kg. The most common treatment-related adverse events were peripheral neuropathy, nausea, fatigue, diarrhea, dizziness, and neutropenia; most were grade 1 or 2 in severity. Exposure to brentuximab vedotin (AUC) increased relative to dose level. Among efficacy evaluable patients across all dose levels, the objective response rate (ORR) was 46% (16 of 35), with 29% of patients (10 of 35) attaining a complete remission. Median duration of response to date is at least 16 weeks (range, 0.1+ to 34+); 15 patients continue on treatment. Conclusions: Weekly dosing with brentuximab vedotin was generally well tolerated and induced a high rate of objective responses in heavily pretreated patients with HL and systemic ALCL. A pivotal trial of this ADC in patients with relapsed or refractory HL has completed enrollment. Disclosures: Fanale: Seattle Genetics, Inc.: Research Funding. Off Label Use: Brentuximab vedotin is an investigational agent. Bartlett:Seattle Genetics, Inc.: Research Funding. Forero-Torres:Seattle Genetics, Inc.: Research Funding. Rosenblatt:Seattle Genetics, Inc.: Research Funding. Horning:Seattle Genetics, Inc.: Research Funding. Franklin:Seattle Genetics, Inc.: Research Funding. Lynch:Seattle Genetics, Inc.: Employment. Sievers:Seattle Genetics, Inc.: Employment, Equity Ownership. Kennedy:Seattle Genetics, Inc.: Employment.

Anti CD-30 Antibody-Drug Conjugate Brentuximab Vedotin (ADCETRIS®) May Be a Promising Treatment Option for Systemic Mastocytosis (SM).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2857-2857 ◽  
Author(s):  
Amitkumar Mehta ◽  
Vishnu V B Reddy ◽  
Uma Borate
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
White Male ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Antimitotic Agent ◽  
Drug Conjugate ◽  
Tryptase Level ◽  
Antibody Drug

Abstract Abstract 2857 Mastocytosis is a clonal proliferation of abnormal mast cells in single or multiple organs leading to clinical syndromes ranging from a benign self-resolving cutaneous disease to the highly aggressive malignancy, mast cell leukemia (MCL). Mastocytosis is categorized under myeloproliferative neoplasms in the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid diseases. In almost all cases of SM, the bone marrow (BM) is involved by atypical mast cells. The characteristic Asp816Val (D816V) mutation in the KIT gene present in most cases gives the atypical mast cells a survival advantage that leads to treatment resistance with tyrosine kinase inhibitor (TKIs) like imatinib. According to the 2008 WHO classification, 1 major and 1 minor or 3 minor criterion are required for the diagnosis of systemic mastocytosis (Fig. 1a). Systemic Mastocytosis (SM) is subcategorized into four distinct categories in order of indolent to highly aggressive disease: Indolent Systemic Mastocytosis (ISM), SM with an associated hematologic non-MC-lineage disease (SM-AHNMD), aggressive SM (ASM) and MCL. SM with C findings categorized as ASM (Fig. 1b) is treated with cytoreductive chemotherapy such as interferon 2α or 2-chlorodeoxyadenosine (2-CdA). The overall response rate (ORR) with these agents is 40–50% with significant chemotherapy-related toxicity and short durable responses. The majority of patients with ASM and MCL relapse within a year with a very poor prognosis. The CD30 (Ki-1) antigen is expressed in the majority of ASM cases. Thus, CD30 can serve as a potential therapeutic target as well as a reliable tumor marker to follow disease status. Brentuximab vedotin is an antibody-drug conjugate compound consisting of a chimeric monoclonal antibody against CD30 linked to the antimitotic agent monomethyl auristatin E (MMAE). Here we report evidence of anti-tumor activity in two patients with CD30-positive ASM treated with brentuximab vedotin. Case #1: A 62 year old white male with significant medical history of rheumatoid arthritis, diabetes mellitus and coronary artery disease was evaluated for pancytopenia and hepatomegaly. His initial BM aspiration and biopsy revealed multifocal dense mast cell infiltrate (30–40% involvement with tryptase and CD117 positivity). His initial serum tryptase level was 276 ng/ml. He was treated with 2-CdA continuous infusion for three cycles with no significant response and substantial toxicities. He was subsequently enrolled in a clinical trial with brentuximab vedotin given every 3 weeks at 1.8 mg/kg after confirmation of CD30 positivity on BM aspirate and biopsy (Fig. 2). His peripheral blood counts started to improve after the 5thcycle and he had a durable partial response as assessed by his peripheral blood counts and BM biopsies (Fig 2). Importantly, his sequential bone marrow biopsies showed a decrease in mast cell involvement and CD30 intensity with improved normal marrow cellularity (Fig 2). His only treatment-related toxicities were grade II neuropathy and neutropenia for which his dose was reduced to 1.2 mg/kg. He is currently asymptomatic with ECOG performance status of 0 and does not require any growth factor support at Cycle 12 of this regimen. Case #2: A 79 yr old white male with significant medical history of hypertension, obstructive sleep apnea, coronary artery disease s/p CABG was referred for new diagnosis of ASM on BM biopsy (60–70% marrow involvement with 3+ mast cell density). His initial tryptase level was 224ng/ml. He was enrolled on the same clinical protocol as described above. His sequential BM biopsies revealed significant reduction in mast cell density with mild improvement in overall normal cellularity after 3 cycles of treatment. (Fig 3). Conclusion: Brentuximab vedotin is a promising targeted therapy for SM and needs to be confirmed further by a prospective multicenter clinical trial. In two patients reported here treatment is well tolerated, targets the malignant mast cells and seems to prevent disease progression in a rare disorder with few treatment options and limited response rates. Disclosures: Off Label Use: Brentuximab vedotin (ADCETRIS®) is an antibody-drug conjugate compound consisting of a chimeric monoclonal antibody against CD30 linked to the antimitotic agent monomethyl auristatin E (MMAE). It is not FDA approved for use in Mastocytosis.

Epratuzumab–SN-38: A New Antibody–Drug Conjugate for the Therapy of Hematologic Malignancies

2011 ◽  
Vol 11 (1) ◽  
pp. 224-234 ◽  
Author(s):  
Robert M. Sharkey ◽  
Serengulam V. Govindan ◽  
Thomas M. Cardillo ◽  
David M. Goldenberg
Keyword(s):  
Hematologic Malignancies ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

scholarly journals Brentuximab vedotin, an antibody–drug conjugate, in patients with CD30‐positive haematologic malignancies and hepatic or renal impairment

2016 ◽  
Vol 82 (3) ◽  
pp. 696-705 ◽  
Author(s):  
Baiteng Zhao ◽  
Robert Chen ◽  
Owen A. O'Connor ◽  
Ajay K. Gopal ◽  
Radhakrishnan Ramchandren ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug ◽  
Haematologic Malignancies
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