FDA Approval: Daratumumab (Darzalex) for Multiple myeloma

An antibody against a marker on the cell surface

Daratumumab, sold as Darzalex, carries an Initial U.S. Approval date of 2015 on its FDA label. It treats multiple myeloma.

It is a monoclonal antibody. That means a lab-made protein that latches onto one target. Its target is CD38, a protein found in large amounts on myeloma cells. Once bound, it marks the cell for the immune system to destroy.

That places it closer to immunotherapy than to old-style chemotherapy. Chemotherapy damages dividing cells broadly.

Where it sits in a regimen

Daratumumab is rarely used alone. NCI lists it as approved, alone or with other drugs, for multiple myeloma in newly diagnosed and in relapsed or refractory disease. Refractory means the disease did not respond to a treatment.

For newly diagnosed disease, NCI describes two paths. One is for people who cannot have a stem cell transplant using their own cells. There the drug is paired with lenalidomide and dexamethasone. It can also be paired with bortezomib, melphalan, and prednisone. The other path is for people who can have that transplant. There it is paired with bortezomib, thalidomide, and dexamethasone.

For relapsed or refractory disease, the mix depends on how many prior therapies a person has had. After at least one, it can be given with dexamethasone and bortezomib. After one to three, it can be given with dexamethasone and carfilzomib. After at least two that included lenalidomide and a proteasome inhibitor, it can be given with pomalidomide and dexamethasone. After at least three types of therapy, it can be given alone.

A second version exists, combined with hyaluronidase, which allows injection under the skin instead of an infusion into a vein.

What multiple myeloma is

Plasma cells are white blood cells that make antibodies. They develop from B lymphocytes in the bone marrow. In multiple myeloma, abnormal plasma cells build up in the marrow and form tumors in many bones.

Those cells make an antibody protein called M protein, which the body does not need and which does not fight infection. M protein builds up in the marrow, can thicken the blood, and can damage the kidneys. The myeloma cells also damage and weaken bone, and they crowd out production of healthy red cells, white cells, and platelets.

Myeloma sits in a family of plasma cell neoplasms. Monoclonal gammopathy of undetermined significance, or MGUS, is not cancer but can become cancer. Plasmacytoma and multiple myeloma are cancers.

When to get checked

Sometimes myeloma causes nothing at all. That form is called smoldering multiple myeloma, and it is often found when a blood or urine test is done for another reason.

NCI says to check with a doctor for:

• Bone pain, especially in the back or ribs.
• Bones that break easily.
• Fever for no known reason, or frequent infections.
• Easy bruising or bleeding.
• Trouble breathing.
• Weakness of the arms or legs.
• Feeling very tired.

A second cluster comes from too much calcium in the blood. Doctors call this hypercalcemia. Myeloma causes it by breaking down bone. Watch for loss of appetite, nausea, vomiting, or thirst. Watch for frequent urination and constipation. Watch for muscle weakness, restlessness, and confusion. It can affect the kidneys, nerves, heart, muscles, and gut. It needs prompt attention.

There is no screening program for myeloma in people without symptoms.

Marrow, blood, urine, and a stage built from two lab values

Tests of blood, bone marrow, and urine make the diagnosis. Bone marrow is sampled to see what fraction of it is abnormal plasma cells.

Staging is unusual here. It does not depend on tumor size or spread. NCI states that the stage of multiple myeloma is based on the levels of beta-2-microglobulin and albumin in the blood, producing stage I, II, or III. Imaging still matters for bone damage. A skeletal bone survey X-rays all the bones, MRI looks at marrow in detail, and bone densitometry measures bone density.

MGUS and plasmacytoma have no standard staging system at all.

Combinations, cycles, and transplant

Treatment is built from combinations. Usually three or four drugs are given at once, in cycles. The main classes are proteasome inhibitors, such as bortezomib. Next are immunomodulating drugs, such as lenalidomide. Then steroids, such as dexamethasone. And last, antibodies, such as this one.

For people who are fit enough, high-dose therapy with a stem cell transplant may follow the first combination. Supportive care runs alongside all of it. That means drugs to protect bone, treatment for high calcium, infection prevention, and kidney checks.

Numbers, and why myeloma stages read strangely

These SEER figures describe the whole US population with myeloma and do not predict any one person's course.

Five-year relative survival for myeloma is 63.7 percent for cases from 2016 to 2022. An estimated 36,000 new cases and 10,850 deaths are projected for 2026 by the American Cancer Society, whose figures SEER lists. Median age at diagnosis is 69.

SEER's stage groups fit myeloma poorly. It is a marrow disease, present in many bones from the start. In SEER's system, 96 percent of cases from 2016 to 2022 are recorded as distant. Five-year relative survival in that group is 63.0 percent. That is nothing like what distant means for a solid tumor. Check what a statistic counts before comparing it across cancers.

What this approval cannot tell you

An approval defines eligible groups in general terms. It does not say which combination is right for one person. Myeloma plans are chosen from a long menu. The choice turns on transplant eligibility, kidney function, prior treatments, and tolerance.

The drug is given by infusion or by injection, on a schedule that changes over time. Infusion reactions are a known issue, above all with the first dose. Our page on multiple myeloma covers the disease in more depth.

Sources

• NCI, Daratumumab — https://www.cancer.gov/about-cancer/treatment/drugs/daratumumab
• DailyMed, DARZALEX (daratumumab) label, Initial U.S. Approval 2015 — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d0efe9-5e54-467e-9eb4-56fa7d53b60b
• NCI PDQ, Plasma Cell Neoplasms Including Multiple Myeloma Treatment (Patient Version) — https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq
• SEER Cancer Stat Facts, Myeloma — https://seer.cancer.gov/statfacts/html/mulmy.html
• NCI, Multiple Myeloma and Other Plasma Cell Neoplasms — https://www.cancer.gov/types/myeloma

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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