Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma, Hodgkin lymphoma and non-Hodgkin lymphoma; both express CD30.
CLASSICAL HODGKIN LYMPHOMA
Classical Hodgkin lymphoma is a type of Hodgkin lymphoma characterized by an abnormal type of B lymphocyte called Reed Sternberg cells. It accounts for 90 to 95 percent of Hodgkin lymphoma. Brentuximab vedotin (Adcetris®) was approved by the Food and Drug Administration (FDA) on August 19, 2011, for the treatment of individuals with Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (HSCT) or after failure of at least two prior multi-agent chemotherapy treatments in individuals who are not candidates for autologous HSCT.
On August 17, 2015, the FDA-approved label was updated to allow brentuximab vedotin (Adcetris®) for the treatment of individuals with Classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two prior multi-agent chemotherapy treatments in individuals who are not candidates for autologous HSCT.
Brentuximab vedotin (Adcetris®) is an antibody-drug conjugate designed to target tumor cells expressing CD30, a tumor necrosis factor (TNF) receptor. The antibody-drug conjugate binds with the CD30, and a small molecule chemotherapeutic agent (monomethyl auristatin [MMAE]) is released. The MMAE causes cell cycle arrest and cell death.
FDA approval for brentuximab vedotin (Adcetris®) was supported by a multi-center phase two trial involving 102 study participants with Hodgkin lymphoma who had received a median of five prior therapies, including autologous stem cell transplant. These participants received the recommended dose and schedule of brentuximab vedotin (Adcetris®), which is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks for a maximum of 16 cycles. Results showed that 73 percent experienced complete or partial response rate after treatment.
On August 17, 2015 brentuximab vedotin (Adcetris®) was approved for the treatment of individuals with classical Hodgkin lymphoma at high risk of relapse or progression as post auto-hematopoietic stem cell transplantation consolidation, treatment given after the cancer has disappeared following the initial therapy. The efficacy of brentuximab vedotin (Adcetris®) in this population was studied in a randomized, double-blind, placebo-controlled clinical trial of 329 individuals. The brentuximab vedotin (Adcetris®) group received 1.8mg/kg intravenously over 30 minutes every 3 weeks for up to 16 cycles. The primary endpoint was progression-free survival determined by an independent review facility. High risk of relapse or progression was defined by status following first-line therapy: refractory, relapse within 12 months, or relapse at 12 months or later with extranodal disease. The brentuximab vedotin (Adcetris®) group had a statistically significant improvement in progression-free survival than the placebo group (42.9 median months vs. 24.1 median months).
On March 20, 2018 brentuximab vedotin (Adcetris®) was approved for the treatment of individuals with previously untreated stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. The approval for adult individuals with previously untreated stage III or IV cHL was based on a clinical trial comparing Adcetris plus chemotherapy, AVD regimen (Adriamycin [doxorubicin], vinblastine and dacarbazine) to a chemotherapy-only regimen common for cHL treatment (AVD plus bleomycin, also known as ABVD). The trial measured modified progression-free survival (mPFS), which considers the length of time it took for the disease to progress, death to occur, or new therapy to be initiated in individuals who did not achieve a complete response. In the trial of 1,334 individuals, after individuals received an average of six 28-day cycles of treatment, those treated with Adcetris plus AVD were 23 percent less likely to experience progression, death, or initiation of new therapy compared with those receiving ABVD. There were 117 (18 percent) individuals on the Adcetris plus AVD arm who experienced disease progression, death, or began new therapy compared to 146 (22 percent) individuals on the ABVD arm.
SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA
Anaplastic large cell lymphoma is a rare form of indolent (slow growing) non-Hodgkin lymphoma. It accounts for 1 in 50 cases of non-Hodgkin lymphoma and is more common in children and men. This cancer often affects the lymph nodes, skin, liver, lungs, and bone marrow. This disease can be systemic (occurring throughout the body) or cutaneous (occurring in or on the skin).
Systemic anaplastic large cell lymphoma is a type of T-cell non-Hodgkin lymphoma that expresses the CD30 antigen. It occurs in both nodal and extranodal locations. Conventional first-line combination chemotherapy regimens used to treat systemic anaplastic large cell lymphoma often result in long-term remissions and sometimes cures; however, there are limited therapeutic options for individuals with relapsed or refractory disease. First-line chemotherapy regimen includes CHOP (cyclophosphamide, hydroxydoxorubicin [doxorubicin], oncovin [Vincristine], prednisone).
Brentuximab vedotin (Adcetris®) was also approved by the FDA on August 19, 2011, for treatment of individuals with systemic anaplastic large cell lymphoma, a type of non-Hodgkin lymphoma, after failing at least one prior multi-agent chemotherapy regimen. The FDA approval of brentuximab vedotin (Adcetris®) for systemic anaplastic large cell lymphoma was based on a phase two open-label, single-arm, multi-center trial involving 58 individuals who experienced a relapse of systemic anaplastic large cell lymphoma after receiving a median of two prior therapies. Eighty-six percent of study participants experienced a complete or partial response rate after treatment with brentuximab vedotin (Adcetris®).
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