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Management of relapsed or refractory hodgkin lymphoma with second-generation antibody-drug conjugates: focus on brentuximab vedotin.

ABSTRACT: Brentuximab vedotin (Adcetris, Seattle Genetics) is an antibody-drug conjugate (ADC) that joins an anti-CD 30 monoclonal antibody with the anti-tubulin agent monomethyl auristatin E via a dipeptide linker. It has demonstrated significant activity in CD 30-positive lymphomas and is currently approved by the US FDA for treatment of Hodgkin lymphoma that has relapsed following autologous stem-cell transplantation, or after two lines of chemotherapy in non-transplant candidates. Brentuximab vedotin has also been approved for the treatment of relapsed anaplastic large-cell lymphoma after front-line chemotherapy. We briefly review the biology of Hodgkin lymphoma, with a focus on the pathogenic role of CD 30 as well as the development of CD 30-targeted therapy. We also discuss both the current role of brentuximab vedotin in the management of relapsed and refractory Hodgkin lymphoma and the likely future developments for this agent.

SUBMITTER: Mei M

PROVIDER: S-EPMC4029876 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Management of relapsed or refractory hodgkin lymphoma with second-generation antibody-drug conjugates: focus on brentuximab vedotin.

Mei Matthew M Thomas Sandra S Chen Robert R

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20140601 3

Brentuximab vedotin (Adcetris, Seattle Genetics) is an antibody-drug conjugate (ADC) that joins an anti-CD 30 monoclonal antibody with the anti-tubulin agent monomethyl auristatin E via a dipeptide linker. It has demonstrated significant activity in CD 30-positive lymphomas and is currently approved by the US FDA for treatment of Hodgkin lymphoma that has relapsed following autologous stem-cell transplantation, or after two lines of chemotherapy in non-transplant candidates. Brentuximab vedotin ...[more]

PMID: 24258497

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Project description:BackgroundWe previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here, we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized.Patients and methodsPatients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles. Patients in complete remission (CR) after two cycles received two additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV.ResultsOf the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the overall response rate (ORR) to second-line BV was 75% with 43% CR. Twenty-eight (50%) patients proceeded directly to AHCT without post-BV chemotherapy, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n = 37) was 71% compared with 54% in patients not in CR (p = 0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%.ConclusionsSecond-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Dataset Information

Management of relapsed or refractory hodgkin lymphoma with second-generation antibody-drug conjugates: focus on brentuximab vedotin.

Publications

Management of relapsed or refractory hodgkin lymphoma with second-generation antibody-drug conjugates: focus on brentuximab vedotin.

Similar Datasets

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