Eplinky Shows Promise for Some Difficult to Treat Lymphoma
- A drug called epcoritamab (brand name: Epkinly) has been approved for the treatment of diffuse large B-cell lymphoma (DLBCL).
- While generally treatable, some cases of DLBCL can be treatment-resistant or can return after an initial cure. These can be a challenge to treat.
- Epkinly is a bispecific antibody that brings the cancerous B cells into contact with T-cells, which can eliminate cancers.
- In a study, 61% of the patients had some response and 38% of the patients had a complete response to the drug. This response lasted an average of 15.6 months.
- Epkinly can lead to side effects, some of which can be severe, and eligible patients should carefully weigh risks vs. benefits with their doctors.
While generally treatable and curable, some cases of DLBCL are resistant to common treatments, or the disease can recur after initially being declared cured. These cases can be particularly challenging to treat.
Read MoreWhat are Lymphomas?
A lymphoma is a blood cancer that originates in the lymphocytes, more commonly known as white blood cells. These cells are produced in the bone marrow, which is the soft, spongy tissue that lines the inner parts of many long bones, including hip bones and vertebral column. White blood cell cancers are sorted into two main categories, leukemias, and lymphomas. Whether a cancer is a leukemia or a lymphoma depends on where the cancerous cells reside.The leukemic cancer cells originate in the bone marrow and circulate within the blood. The lymphoma cancer cells, on the other hand, live within the lymph nodes and the lymphatic system. They often cause the lymph nodes to enlarge, forming masses that can be felt or even seen in lymphoma patients.
The lymphatic system is an extensive network of tissues throughout the body. It includes lymph nodes, which are rounded collections of white blood cells resembling beans. These nodes are interconnected through lymphatic channels. Lymphatic tissue is also present in the spleen, bone marrow, thymus gland, gastrointestinal tract, and other locations. Lymphomas can develop in any of these areas.
RELATED: Non-Hodgkin Lymphoma: Overview
Lymphomas are further divided into Hodgkin vs. non-Hodgkin lymphomas depending on a variety of characteristics. These characteristics include the appearance of the cancer cells under a microscope (pathology), such as the presence of Reed-Sternberg cells (typical of Hodgkin lymphomas) under a microscope, disease staging and spread, patient outcomes, and treatment approaches.
What is Diffuse Large B-cell Lymphoma?
Diffuse Large B-cell Lymphomas (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for almost 1/3rd of all cases.
These lymphomas start in the B lymphocytes, a type of white blood cell. A workhorse of the human immune system, B lymphocytes are responsible for producing antibodies that fend off infections. They are also responsible for immunologic memory, where exposure to a specific antigen trains the immune system to tackle it more efficiently and speedily in the future.
DLBCL occurs when B lymphocytes grow rapidly and haphazardly. This growth can happen in the lymph nodes or any other part of the lymphatic system, including the bone marrow and spleen. Sometimes organs that are not typically included in the lymphatic system, such as the liver, can also be involved.
DLBCL is not treated with a one-size-fits-all approach. Treatment may involve a combination of chemotherapy, immunotherapy, and radiation depending on the specific nature of a patient's disease, their ability to tolerate potentially toxic treatments, and their overall health.
What is Relapsed or Refractory Diffuse Large B-cell Lymphoma?
DLBCL is usually a highly treatable disease, with most of the patients achieving long-term cure or remission. However, despite treatment and initial cure, the disease can return in the future and is called relapsed DLBCL. Sometimes, DLBCL treatment can prove unresponsive to common treatments and is termed refractory.
The treatment success rate for relapsed or refractory cases can vary but is generally lower than those who achieve a cure with initial treatment. Thus, there is a continued need for new treatments that can address such cases.
How Can Epkinly Help?
Epkinly (epcoritamab) is a bispecific antibody.
Naturally occurring antibodies are Y-shaped proteins. The two arms at the top of the Y shape usually bind to two identical molecules, the so-called antigen, which is normally present on disease-causing agents, such as bacteria and fungi. This binding usually springs the immune system into action, which ultimately results in the elimination of the offending agent.
Bispecific antibodies are laboratory-engineered. In contrast to natural antibodies, their two arms can bind two different targets, one of which is usually the cancer cell and the other is an immune system cell, like a T cell. In the case of Epkinly, one arm binds to a protein called CD20 on the malignant B cells while the other arm binds to a protein called CD3 on T cells.
A bispecific antibody is an antibody that has at least two arms, usually one to [bind] to a T-cell, and one to [bind] to a tumor target, Dr. Catherine Diefenbach, Director of the Clinical Lymphoma program at Perlmutter Cancer Center, previously told SurvivorNet.
Dr. Catherine Diefenbach explains how bispecific antibodies work.
T-cells are the body’s main defense mechanism against cancer. Yet these cells can commonly be fooled by the cancer cells into thinking that cancer cells are just normal body cells that should not be destroyed.
There are many ways in which cancer cells commit this deceit. They may start to express some of the same proteins as normal body cells, which blind the T-cells to the true nature of the cancer cells.
RELATED: Bispecific Antibodies Deliver One-Two Punch to Non-Hodgkin Lymphoma
However, when bispecific antibodies engage cancer and T cell at once, they activate the latter, forcing them into action against the former. This culminates in the immune system mounting an attack on the cancer, eventually eliminating it from the body,
Study Shows Efficacy of Epkinly
Researchers from Denmark, the Netherlands, Spain, the United Kingdom, and the United States, tested the drug in patients with relapsed/refractory DLBCL in a recent phase I/II trial (EPCORE NHL-1). They treated 148 patients with epcoritamab (Eplinky) and measured their objective response rates (ORR).
ORR is a measure of treatment efficacy. Expressed as a percentage, ORR is a measure of the patients who achieve a significant positive response to the treatment. This can either be a complete disappearance of the disease (complete response) or a reduction in the disease burden (partial response).
In the epcoritamab (Epkinly) trial, 61% of the patients achieved a partial response and 38% of the patients had a complete response. The duration of this response, on average, was 15.6 months.
“The response rates are high, including among some high-risk patient subgroups, and appear to be durable, but we only have one year of follow-up so far,” Dr. Reid Merryman, of the Dana-Farber Cancer Institute, said of using epcoritamab (Epkinly) to treat certain lymphoma patients.
“We need to follow these patients longer and see how durable these remissions are, but at this point, the data are very encouraging,” he added.
Epkinly Carries Side Effects
The drug carries a risk of side effects, some of which can be severe or life-threatening.
Some common side effects include:
- Tiredness
- Muscle and joint pain
- Pain at the injection site (the medication is given subcutaneously)
- Nausea
- Diarrhea
- Fever
- Abdominal pain
- Cytokine release syndrome (CRS)
CRS, which occurs when the body’s immune system responds to drugs more aggressively than it should, has been observed in 51% of the patients taking Eplinky. Cytokines are signaling molecules used by the immune system to coordinate an immune response. However, when bispecific antibodies are used, they can over-activate the immune system, resulting in the release of abnormal amounts of cytokines into the bloodstream.
This can commonly present as fatigue, fever, and muscle and joint aches. When severe, it can cause difficulty breathing, dangerously low blood pressure, or even be life-threatening.
Another serious but less common side effect of the medication is immune effector cell-associated neurotoxicity syndrome (ICANS). Observed in up to 6% of the patients, this syndrome affects the central nervous system and can cause symptoms like headaches, seizures, confusion, delirium, tremors, come, and in severe cases, death.
Questions To Ask Your Doctor:
- Am I a good candidate for epcoritamab (Epkinly)?
- What are my chances of achieving a good response to this medication?
- What are my other treatment options?
- What side effects will I experience while taking the drug?
- Am I at risk for the more serious, life-threatening side effects of the drug?
- What can I do to minimize these side effects?
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