also known as cAC10 primarily targets the cell-membrane protein CD30 present on
lymphoma cells. MMAE is highly toxic and hence stably linked to brentuximab so
that the drug is not easily released from the antibody in physiological
conditions lest it imparts its toxicity to healthy cells. This binding also
ensures that the dosage of the drug is maintained till it enters the target
‘An antibody-drug conjugate known as Adcetris has been approved for previously untreated stage III or IV classical Hodgkin lymphoma in combination with chemotherapy.’
is predominantly present only on diseased cells and rarely on normal tissues. Once the conjugate reaches the tumor cells,
the antibody cAC10 part binds to CD30 on the surface of malignant cells.
conjugate is then internalized by endocytosis and forms a vesicle which fuses
with lysosomes. MMAE is rapidly and
efficiently cleaved, releasing the drug into the tumor environment.
this trial, Adcetris was approved by the FDA to treat cHL after relapse, cHL
when a patient is at high risk of relapse or
progression, and for systemic anaplastic large cell lymphoma (ALCL) and primary
cutaneous ALCL after failure of other treatments.
Phase 3 clinical trial
total of 1334 patients who had not been previously treated for Hodgkin's lymphoma
enrolled in the trial. They were
assigned to 2 groups and received an average of six 28-day cycles of treatment.
The primary endpoint was
progression-free survival (mPFS)
- A group of 664 patients received A+AVD (Adcetris plus chemotherapy of adriamycin
(doxorubicin), vinblastine and dacarbazine)
- The second group of 670 patients received the
standard-of-care / chemotherapy-only regimen (AVD plus bleomycin, also
known as ABVD)
which takes into account the time taken for
- The disease to progress
- Death to occur
- New therapy to be initiated in patients with
Neutropenia and peripheral
- Those treated with A+ AVD were 23 percent less likely to
experience disease progression, death or begin new therapy compared to
those receiving ABVD
- There were 82 percent of patients in the A+AVD who did not
experience disease progression, death or begin new therapy compared to 77
percent in the ABVD group
- Adverse events like low levels of white blood cells (neutropenia)
and nerve damage causing numbness or weakness in the hands and feet
(peripheral neuropathy) occurred more commonly in the A+AVD group than in
the ABVD group.
are listed among the common
of Adcetris along with anemia, nausea, fatigue, diarrhea and
Due to the risk
of neutropenia, patients taking Adcetris plus chemotherapy are recommended to
take a growth factor, G-CSF as a preventive treatment to make the bone marrow
produce more white blood cells.
of Adcertis include allergic
or infusion-site reactions, damage to the blood, lungs, and liver, metabolic
abnormalities and severe skin and gastrointestinal complications
Adcetris has a boxed warning
that highlights the risk of John Cunningham
virus infection that can result in a rare but potentially fatal brain infection
known as progressive multifocal leukoencephalopathy or PML.
"Today's approval represents an
improvement in the initial treatment regimens of advanced Hodgkin lymphoma that
were introduced into clinical practice more than 40 years ago," said Richard
Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting
director of the Office of Hematology and Oncology Products in the FDA's Center
for Drug Evaluation and Research. "This approval demonstrates our commitment to
approving advancements in treatment that give prescribers and patients'
different options for care."
Hodgkin Lymphoma (cHL)
Hodgkin lymphoma or Hodgkin disease
is a type of lymphoma
a cancer that begins in the lymph system, which is part of the immune system.
Lymphoma can begin almost anywhere in the body and can spread to nearby lymph
nodes. The other main type of lymphoma is the non-Hodgkin lymphoma. Most people with Hodgkin lymphoma have the
classical type that is characterized by large, abnormal lymphocytes (a type of
white blood cell) in the lymph nodes called Reed-Sternberg cells
. If early
intervention is given, patients with Hodgkin lymphoma can usually experience
As of 2018, the number of new cases of cHL in the United States is about
8,500, and the number of deaths from this cancer is about 1,050.
- FDA expands approval of Adcetris for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy - (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm601935.htm)
- Brentuximab vedotin - (https://en.wikipedia.org/wiki/Brentuximab_vedotin)