A CD30 directed antibody drug-conjugate for the treatment of Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma, after other treatments have failed.
Tradename Adcentris.
An antibody-drug conjugate that delivers the microtubule-disrupting agent monoethyl auristatin E (MMAE) to CD 30 positive cells.
A transmembrane glycoprotein receptor and member of the tumor necrosis factor receptor super family.
Binding to CD30 leads to internalization of the congugate and endocytosis into a lysosome, where proteases release the monmethyl auristatin.
Subsequent to the binding of monomethyl auristatin E to tubulin induces cell cycle arrest and apoptosis.
CD30 is expressed in many lymphomas while having very low expression on normal tissue.
In healthy tissue, the majority of CD30 expression is limited to activated B cells, T cells, and natural killer cells, although activated lymphocytes make up those than 1% of the circulating cells in the blood.
CD30 is universally expressed in classical Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma, as well as primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis.
Presently it is approved for patients with HD who have relapsed after ASCT or experience refractory/relapsing disease after at least two prior multiagent chemotherapy regimens and who are not ASCT candidates.
In trial of relapsed or refractory HD patients after ASCT, response rate of 75% with 34% complete responses (Young A et al).
Considered an efficient treatment treatment regimen, which has successfully used as a bridge to transplant, either ASCT or allo-SCT.
An alternative is it can be used as a maintenance agent after ASCT in patients with high risk of failure after ASCT (AETHERA trial).
ECHELON-1 compared ABVD to AVD plus brentuximab in untreated Classic HD stage III/IV for up to 6 cycles: At 2 years the brentuximab group had PFS of 82.1% vs 77.2%, with a 23% lower risk of progression,and death.
In the Echelon-1 trial there was a higher degree of peripheral neuropathyin the brentuximab arm than in the ABVD arm.
Neurotoxicity can be severe and impaired quality of life.
Now indicated for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
FDA approval was based in part on the clinical trial results from ALCANZA, a global, phase 3, randomized study evaluating methotrexate or bexarotene.
Chemical leakage of antibody against CD30 protein with monomethyl auristatin E.
First treatment specifically indicated for anaplastic large cell lymphoma.
In Hodgkin’s disease indicated after failure of autologous stem cell transplant or after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not autologous stem cell transplant candidates.
Myelosuppression and peripheral neuropathy are the most common severe adverse effects.
In refractory HD patients the response rate is 75%, with 34% complete remission and 94% of patients experienced some reduction in tumor burden, and a progression free survival of longer than seven months (Chen R et al).
Approved as frontline combination with chemo therapy for patients with stage 3/4 classical Hodgkin’s lymphoma.
Brentuximab plus doxorubicin, vinblastine , and dacarbazine (A-AVD) had a 5.1% benefit over a ABVD a difference of 10.6% in progression free survival at two years.
Induces objective response rates of 75% in patients with relapsed or refractory Hodgkin’s lymphoma after autologous stem cell transplant.
In anaplastic large cell lymphoma, a trial of 58 patient’s was associated with a 86% response rate and a complete remission rate of 53% with a median duration of response of 12.6 months.
May be associated with the development of progressive multifocal leukoencephalopathy.
In a phase I study exploring the first-line use of brentuximab vedotin in treatment of patients with CD30-positive Hodgkin’s lymphoma: pulmonary toxicity in the brentuximab plus ABVD arm was 44%, and no patients experienced this toxicity with brentuximab plus AVD.
The results definitely confirm that further combination of brentuximab and bleomycin is not advised.
Concomitant use with bleomycin increases the risk of pulmonary toxicity.
Associated with thrombocytopenia, and hyperglycemia.
Dose 1.8 mg/kg infusion every three weeks.
Brentuximab has an overall response rate of 70% in refractory/advanced mycosis fungoides and Sezary syndrome.
In front line therapy for elderly patients with Hodgkin’s disease the overall response rate is 92% with 73% achieving complete remission and 19% achieving partial remission: This agent is an option for elderly patients.
In a study of patients with Hodgkin’s disease unsuitable for chemotherapy the median progression free survival was 7.4 months, complete response rte 26%with an overall response rte of 84% in 38 patients (BREVITY study).
AETHERA trial tested the use of Brentuximab in patients that have undergone an autologous stem cell transplant and received maintenance Brentuximab-progression free survival was 61% at 3 years compared to 43% for placebo.
Research has demonstrated that brentuximab vedotin has helped improve the prognosis and survival of patients with Hodgkin lymphoma who had relapsed after stem cell transplantation or had refractory disease.
Overall response rate was 60.9%.
Stable disease was in 10.9% and progression was observed in 28.1% .
Progression-free survival (PFS) for the patient population was 14 months.
For patients with a complete or partial response to therapy, the median PFS was not reached by the end of the analysis, but patients with stable disease or progression had an event-free survival of 7 months.
It is most effective in patients with chemotherapy-sensitive disease and when used as a consolidation therapy immediately after ASCT.
Research has demonstrated that brentuximab vedotin has helped improve the prognosis and survival of patients with Hodgkin lymphoma who had relapsed after stem cell transplantation or had refractory disease.
Overall response rate was 60.9%.
Stable disease was in 10.9% and progression was observed in 28.1% .
Progression-free survival (PFS) for the patient population was 14 months.
For patients with a complete or partial response to therapy, the median PFS was not reached by the end of the analysis, but patients with stable disease or progression had an event-free survival of 7 months.
It is most effective in patients with chemotherapy-sensitive disease and when used as a consolidation therapy immediately after ASCT.
In the ALCANZA trial median free survival 16.7 months compared to physicians choice arm for cutaneous t-cell lymphoma (CTCL).
Should be a favored agent in the management in CTCL.
Most common adverse reactions are: peripheral sensory neuropathy, fatigue, nausea, neutropenia, and diarrhea.
Peripheral neuropathy fequently resolves.
Neuropathy is dose dependent, as more doses are given the risk of neuropathy increases.
The greatest risk for peripheral neuropathy occurs at 10-12 doses.
The combination of Brentuximab and nivolumab effective in relapsed or refractory Hodgkin lymphoma.