Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma

The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 03/2012; 30(18):2183-9. DOI: 10.1200/JCO.2011.38.0410
Source: PubMed


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.
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.
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.
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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    • "ADCs combine the cancer-killing properties of the cytotoxic agent with the targeted action of mAbs, resulting in a selective destruction of tumor cells. Brentuximab vedotin is an ADC generated by conjugating the humanized anti-CD30 mAb SGN-30 to the cytotoxic agent monomethyl auristatin E (MMAE); it is approved for relapsed Hodgkin's lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (ALCL) [50] [51] . Trastuzumab emtansine (T-DM1) is another ADC that is approved for the treatment of HER2-positive metastatic breast cancer [52] . "
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    • "Brentuximab vedotin comprises the anti-CD30 monoclonal antibody cAC10 conjugated to the cytotoxic agent monomethyl auristatin E, a synthetic analog of the tubulin polymerization inhibitor dolastatin 10, via linkage to a chimeric immunoglobulin (Ig)G1 antibody formed by partial reduction of interchain disulfide bonds of Ig. Brentuximab vedotin has been granted accelerated conditional approval by the US Food and Drug Administration (FDA) after its efficacy was proven in a single-arm Phase II trial of Hodgkin’s lymphoma patients who had progressed after an autologous stem cell transplant, or in patients who were ineligible for transplant, having progressed on at least two chemotherapy regimens.26 Tumor reductions were seen in 94% of the over 100 patients recruited in the trial. "
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    • "Nevertheless, the patient affected by this adverse event has fully recovered. Our results on 45 patients confirm previous reports on the efficacy of BV in the setting of relapsed or refractory CD30+ lymphoma (Pro et al, 2012; Younes et al, 2012). BV is effective in this heavily pretreated group of patients even though the PFS was short because many responding patients have relapsed. "

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