FDA Approval: Carfilzomib (Kyprolis) for Multiple myeloma

The approval, and the asterisk it carried

FDA approved Kyprolis on July 20, 2012. The drug is carfilzomib. Its file is new drug application 202714. It came in as a new molecular entity with orphan drug status.

The 2012 label is worth reading closely. It set a narrow group. People with myeloma who had already had at least two prior therapies. Those had to include bortezomib and a drug of the class known as immunomodulatory. And the disease had to have grown on or within 60 days of the last one.

Then this sentence: "Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified."

That is accelerated approval. FDA can clear a drug on a measure that is only expected to predict benefit. Here that measure was how many tumors shrank. The maker then has to prove real benefit later.

The follow-through happened. FDA keeps a register of accelerated approvals that went on to confirm benefit. Kyprolis is on it. Accelerated July 20, 2012. Verified January 21, 2016.

What myeloma is

Myeloma is a cancer of plasma cells. Those are the white blood cells that make antibodies. When they turn cancerous they crowd the bone marrow. They also pump out one useless antibody in bulk. That is the M protein, or monoclonal protein, seen on a blood test.

NCI groups myeloma with two related conditions that share the same marker. One is MGUS, short for monoclonal gammopathy of undetermined significance. The other is smoldering myeloma. Both need watching, not treating.

Myeloma that needs treatment is defined by damage. NCI publishes the criteria set by the International Myeloma Working Group. Blood calcium more than 1 mg/dL above the normal range. Creatinine above 2 mg/dL, or creatinine clearance under 40 mL/min. Hemoglobin below 10.0 g/dL. One or more bone lesions on a scan.

Read those four together and the disease makes sense. It raises calcium by dissolving bone. It strains the kidneys with excess protein. It causes anemia by crowding the marrow. And it eats holes in bone. Our page on multiple myeloma goes deeper.

What a proteasome inhibitor does

Every cell has a proteasome. It is a disposal unit that shreds proteins the cell no longer needs. Plasma cells build antibodies at industrial volume. So myeloma cells make huge amounts of protein waste. They lean on that disposal unit harder than most cells do.

Block the proteasome and the garbage piles up. In the end the cell kills itself. That is why this drug class hits myeloma cells harder than healthy ones. Bortezomib was the first of them. Carfilzomib binds more tightly, and it does not let go.

The 2012 label lists what that costs. Warnings covered heart failure and reduced blood flow to the heart. Also high blood pressure in the lung arteries, and breathing problems. Also infusion reactions and low platelets. Also liver toxicity. And tumor lysis syndrome, a flood of contents from dying cells that can harm the kidneys. That is why fluids and a steroid are given first.

What the label says today

This is the part a 2012 news story cannot tell you, and it is why old approval coverage misleads.

The current prescribing information is published through DailyMed. It no longer carries the 2012 wording. Kyprolis is now for adults with relapsed or refractory myeloma who have had one to three prior lines. It is given with a partner drug. The label lists four pairings and also allows use on its own after one or more prior lines.

So the drug moved earlier in the sequence. It also became a combination partner. The 2012 indication is not the one in force.

When myeloma should be considered

Myeloma is rarely the first thought. Its early signs are easy to blame on age.

• Back or rib pain that sticks around, gets worse on movement, and has no injury behind it.
• A bone that broke under a load it should have handled.
• Tiredness with anemia on a blood count. This matters more if total protein is also raised.
• Kidney function that has drifted worse with no clear reason.
• Repeated infections, especially chest infections, in someone not usually prone to them.
• High blood calcium found by chance. It can cause thirst, confusion, and constipation.

The first tests are ordinary. A blood count. Kidney function. Calcium. And protein electrophoresis, which looks for an M protein.

What to keep in perspective

• Accelerated approval on response rate is not proof of survival benefit at the time. For this drug the benefit was later confirmed. That does not happen with every accelerated approval.
• A 2012 approval notice describes a moment, not current practice. Check the label in force.
• SEER, the federal cancer surveillance program, estimates about 36,000 new myeloma cases in the United States in 2026. It estimates about 10,850 deaths. Five-year relative survival is 63.7 percent. That is a group average from people diagnosed years ago. It does not describe an individual.
• Myeloma remains a disease that is controlled rather than cured for most people, through successive lines of treatment.
• The label sets who is eligible. Whether a drug fits one person is a clinical decision, not a reading of a news page.

Sources

• FDA Drugs@FDA overview: KYPROLIS (carfilzomib), NDA 202714
• FDA-approved 2012 label for KYPROLIS (PDF)
• FDA: Verified Clinical Benefit — Cancer Accelerated Approvals
• DailyMed: current KYPROLIS prescribing information (SPL)
• NCI PDQ: Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (Health Professional Version)
• NCI SEER Cancer Stat Facts: 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.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

See an error, old source, or unclear wording? Tell us.