Elotuzumab, sold under the brand name Empliciti, is a humanized IgG1

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

medication used in combination with

lenalidomide Lenalidomide, sold under the brand name Revlimid among others, is a medication used to treat multiple myeloma, smoldering myeloma, and myelodysplastic syndromes (MDS). For multiple myeloma, it is a first-line treatment, and is given with dexa ...

and

dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...

, for adults that have received 1 to 3 prior therapies for the treatment of

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

. It is also indicated for adult patients in combination with

pomalidomide Pomalidomide, sold under the brand names Pomalyst and Imnovid, is an anti-cancer medication used for the treatment of multiple myeloma and AIDS-related Kaposi sarcoma. Pomalidomide was approved for medical use in the United States in February ...

and

, who have received 2 prior therapies including lenalidomide and a protease inhibitor. Administration of elotuzumab is done intravenously. Each intravenous injection of elotuzumab should be premedicated with

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

ranitidine Ranitidine, previously sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It was commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellis ...

and

acetaminophen Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...

. It is being developed by

Bristol Myers Squibb The Bristol-Myers Squibb Company, Trade name, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies ...

and

AbbVie AbbVie Inc. is an American pharmaceutical company headquartered in North Chicago, Illinois. It is ranked sixth on the list of largest biomedical companies by revenue. In 2023, the company's seat in Forbes Global 2000 was 74, and rank 89 on the ...

. Common

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of elotuzumab with lenalidomide and dexamethasone includes

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

pyrexia Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range caused by an increase in the body's temperature set point in the hypothalamus. There is no single agre ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

cough A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and Microorganism, microbes. As a protective reflex, coughing can be repetitive with the cough reflex fol ...

peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

, nasopharyngitis,

upper respiratory tract infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the nose, sinuses, pharynx, larynx or trachea. This commonly includes nasal obstruction, sore throat ...

, decreased appetite, and

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

. The most common side effects of elotuzumab with pomalidomide and dexamethasone includes

and

hyperglycemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

. There is no available information for the use of elotuzumab in

pregnant women Pregnancy is the time during which one or more offspring gestates inside a woman's uterus. A multiple pregnancy involves more than one offspring, such as with twins. Conception usually occurs following vaginal intercourse, but can also ...

. Elotuzumab is an immunostimulatory antibody that targets the Signaling Lymphocytic Activation Molecule Family member 7 ( SLAMF7) through two mechanisms. In May 2014, it was granted

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

designation by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) (for multiple myeloma). The initial

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approval of elotuzumab in 2015 in combination with

and

was carried out through the results illustrated in the ELOQUENT 2 study. In May 2016 the EC/EU gave a similar approval. Furthermore, the results of the ELOQUENT 3 study led to the

approval of elotuzumab in combination with

and

in 2018.

Medical use

Multiple myeloma

Elotuzumab is indicated for adult patients in combination treatment for

in patients that have received 1 to 3 prior therapies. For medical use in multiple myeloma patients, elotuzumab can be combined with either lenalidomide and dexamethasone or pomalidomide and dexamethasone.

Dosage and administration

In combination with lenalidomide and dexamethasone

The package insert advises that intravenous administration with 10 mg/kg every week for the first 2 cycles (each cycle is 28 days) and every 2 weeks thereafter, with the appropriate doses of lenalidomide and low dose dexamethasone is acceptable for treatment. For additional information on dosing dexamethasone and/or lenalidomide, refer to the package inserts.

In combination with pomalidomide and dexamethasone

Elotuzumab is recommended through intravenous administration at 10 mg/kg each week for the first 2 cycles (each cycle is 28 days). At the start of cycle 3, administer 20 mg/kg every 4 weeks, while administering the recommended dose of pomalidomide and low dose dexamethasone. For additional information on dosing dexamethasone and/or dexamethasone, refer to the package inserts.

Adverse effects

To evaluate the adverse reactions in the Eloquent 2 trial, elotuzumab was combined with lenalidomide and dexamethasone and compared with lenalidomide and dexamethasone alone. The most common adverse reactions (20% or higher) denoted in the elotuzumab treated patients in the study were: *

Fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

, nasopharyngitis,

, decreased appetite, and

Similarly, the adverse reactions in the Eloquent 3 trial were examined by comparing the elotuzumab combined with pomalidomide and dexamethasone with the pomalidomide and dexamethasone alone. *

Constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

and

Mechanism of action

Elotuzumab is an immunostimulatory antibody that targets signaling lymphocyte activation molecule family member 7, also known as SLAMF7. SLAMF7 is a cell surface

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

that is present on myeloma cells,

natural killer cell Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells ...

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances ca ...

s, and subsets of immune cells of the

hematopoietic Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...

lineage. Elotuzumab works by activating the

natural killer Nature is an inherent character or constitution, particularly of the ecosphere or the universe as a whole. In this general sense nature refers to the laws, elements and phenomena of the physical world, including life. Although humans are par ...

cells through the SLAMF7 pathway. Along with that, the SLAMF7 of the myeloma cells are targeted and flagged, for natural killer cell-mediated destruction through antibody-dependent cellular toxicity.

Clinical trials

Eloquent 2 trial

The trial, Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma, also known as the Eloquent 2 trial, studied the

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...

and safety of elotuzumab. The objective of the study was to determine if the addition of elotuzumab with

and

would increase

progression-free survival Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is ...

in patients with refractory multiple myeloma. This randomized,

open-label An open-label trial, or open trial, is a type of clinical trial in which information is not withheld from trial participants. In particular, both the researchers and participants know which treatment is being administered. This contrasts with a do ...

, phase 3, multicenter trial studied patients 18 years and older with multiple myeloma and measurable disease. With 321 patients designated to the elotuzumab group and 325 to the

control group In the design of experiments, hypotheses are applied to experimental units in a treatment group. In comparative experiments, members of a control group receive a standard treatment, a placebo, or no treatment at all. There may be more than one tr ...

, the elotuzumab group had a significant relative reduction in the risk of disease progression or death. The median progression-free survival for the elotuzumab group was 19.4 months compared with 14.9 months in the control group. Additionally, the response rate for the etoluzumab group was 79%, compared to the control group with 66%.

Eloquent 3 trial

In the Eloquent 3 trial, also known as Elotuzumab plus

Pomalidomide Pomalidomide, sold under the brand names Pomalyst and Imnovid, is an anti-cancer medication used for the treatment of multiple myeloma and AIDS-related Kaposi sarcoma. Pomalidomide was approved for medical use in the United States in February ...

and

Dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...

for Multiple Myeloma, 117 patients with refractory or relapsed multiple myeloma, and were refractory to lenalidomide and a protease inhibitor, were randomized to either the elotuzumab group or the control group. The elotuzumab group, with 60 patients, received elotuzumab with pomalidomide and dexamethasone and the

, with 57 patients, received pomalidomide and dexamethasone alone. Among patients that had failed treatment with lenalidomide and a protease inhibitor, death or risk of progression was significantly lower in the elotuzumab study arm. The median progression-free survival in the elotuzumab study arm was 10.3 months compared to 4.7 months in the control study group, after a 9.1 month follow up period.

References

{{Portal bar , Medicine Monoclonal antibodies for tumors Drugs developed by Bristol Myers Squibb Drugs developed by AbbVie Orphan drugs