FDA Approval: Lenalidomide (Revlimid) for Multiple myeloma

What myeloma is a cancer of

Plasma cells are the part of the immune system that makes antibodies. They live in the bone marrow. In multiple myeloma, abnormal plasma cells build up there and form tumors in many bones at once.

Two things follow. The marrow gets crowded, so it makes fewer red cells, white cells and platelets. The myeloma cells also damage and weaken bone directly.

NCI notes that myeloma sometimes causes no symptoms. That version is called smoldering myeloma, and it often turns up on a blood or urine test done for something else.

A drug the field almost did not revisit

Lenalidomide is an analogue of thalidomide. Its label states this plainly, and so does the boxed warning.

Thalidomide is one of the most notorious drugs in medicine. It caused severe birth defects, and the label calls it a known human teratogen. Lenalidomide caused limb abnormalities in a developmental study in monkeys.

That history sits on the front of the label. Lenalidomide reaches US patients only through a restricted distribution program, the Lenalidomide REMS. Women of reproductive potential need two negative pregnancy tests before starting. They also need two forms of contraception, or continuous abstinence, during treatment and for four weeks after.

How it works

Lenalidomide binds a protein called cereblon. Cereblon is part of an enzyme complex that tags other proteins for destruction.

With the drug attached, the complex tags proteins it would otherwise leave alone. The label names three: Aiolos, Ikaros and CK1 alpha. Tagged proteins are destroyed, and myeloma cells that depend on them die.

The label also describes immune effects. Lenalidomide raises the number and activity of T cells and natural killer cells. It boosts interleukin-2 and interferon gamma, and damps down inflammatory signals from monocytes. It is antiangiogenic too, meaning it hinders the growth of new blood vessels.

That mix is why lenalidomide is called an immunomodulatory drug and not a chemotherapy.

What the FDA approved, and when

The FDA first approved lenalidomide on December 27, 2005, under application NDA 021880. That was for transfusion-dependent anemia in low-risk myelodysplastic syndromes with a deletion 5q abnormality.

The myeloma approval came six months later. Drugs@FDA records a supplement to the same application approved on June 29, 2006. NCI describes it as lenalidomide with dexamethasone, for people who had already had at least one other therapy.

In 2015 the combination was approved for newly diagnosed myeloma in people not eligible for an autologous stem cell transplant. In that procedure a person's own stem cells are collected, stored, and returned after high-dose treatment.

In March 2017 NCI reported FDA approval of lenalidomide as maintenance after such a transplant. Two randomized double-blind trials backed it: the NCI-funded CALGB 100104 and the European IFM 2005-02. Progression-free survival ran about 19 and 18 months longer than placebo.

The three boxed warnings

The label carries three, and they are not interchangeable.

Embryo-fetal toxicity. The drug must not be used in pregnancy, and the REMS program exists to prevent fetal exposure.

Hematologic toxicity. Lenalidomide causes significant neutropenia, a shortage of infection-fighting white cells, and thrombocytopenia, a shortage of platelets. In the main myelodysplastic syndrome study, 80 percent of patients needed a dose delay or reduction, and 34 percent needed a second one.

Venous and arterial thromboembolism. Blood clots, in veins and arteries.

The maintenance trials added another finding. At more than seven years of median follow-up, second cancers, excluding basal and squamous skin cancers, occurred in 14.9 percent of people on lenalidomide against 8.8 percent on placebo. Our page on chemotherapy and second cancers explains how that kind of risk is weighed.

When to get checked

NCI lists these as reasons to check with a doctor, and notes other conditions cause them too:

• 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.

Bone damage from myeloma can release calcium into the blood. That is hypercalcemia, and NCI lists its own set of signs: loss of appetite, nausea or vomiting, thirst, frequent urination and constipation.

Back pain is close to universal in adults, so it is a poor alarm on its own. The combination is what counts. Back pain plus unexplained tiredness plus repeated infections over a few months, or a bone that breaks from a minor knock, is worth blood tests. Our page on multiple myeloma symptoms sets out what those tests look for.

The population picture

The American Cancer Society's 2026 projection is 36,000 new US myeloma cases and 10,850 deaths, and SEER hosts it. In SEER's own data, median age at diagnosis is 69 and median age at death is 76.

Five-year relative survival for cases from 2016 to 2022 is 63.7 percent. In the mid-1970s the same figure was around 25 percent.

The stage breakdown looks odd next to other cancers. SEER classes 96 percent of myeloma as distant, because myeloma sits in marrow throughout the body by nature rather than by spreading late. Five-year relative survival in that group is 63.0 percent.

These are registry averages. Myeloma outcomes vary widely by genetics, kidney function and age, so no average describes a person. Our page on multiple myeloma covers how those differences are judged.

What to keep in perspective

The 2006 approval covered lenalidomide with dexamethasone, in people who had already had one other treatment. It was not a first-line approval. Later approvals covered different situations.

No approval says the drug is right for a particular person. The label sets the boundary; a clinician decides inside it.

The second-cancer signal from the maintenance trials is real, and it is discussed with patients rather than hidden. It is weighed against myeloma itself, which remains serious.

And the field has moved. Proteasome inhibitors, antibodies against CD38, and cell therapies have all arrived since 2006. Where lenalidomide sits in a modern plan is a current question.

Sources

• FDA Drugs@FDA record for NDA 021880 (Revlimid), showing the myeloma supplement approved 29 June 2006, via the openFDA API — https://api.fda.gov/drug/drugsfda.json?search=application_number:%22NDA021880%22&limit=1
• FDA prescribing information for REVLIMID, via the openFDA drug label API — https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22REVLIMID%22&limit=1
• NCI Cancer Currents, New Use for Lenalidomide in Multiple Myeloma, March 2017 — https://www.cancer.gov/news-events/cancer-currents-blog/2017/fda-lenalidomide-myeloma-maintenance
• 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

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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