Multiple Myeloma

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The Story of Lenalidomide: A Major Advance in Treatment

Dr. Vincent Rajkumar Mayo Clinic

Lenalidomide, also known as its trade name Revlimid, is currently a mainstay in multiple myeloma treatment. In newly diagnosed patients, standard doses of lenalidomide, in combination with other therapies, is used to kill myeloma cells. Later on in treatment, low doses of lenalidomide is used to keep the immune system on high alert in case the cancer begins to come back following chemotherapy.

However, thalidomide, the precursor to lenalidomide, was initially not developed as a treatment for multiple myeloma. “The story of thalidomide is one of the most fascinating stories in all of medicine,” remembers Dr. Vincent Rajkumar, medical oncologist at the Mayo Clinic and one of the key players in getting lenalidomide federally approved for multiple myeloma treatment.  “Thalidomide was developed as a sleeping pill in the late 50s. And when it was developed nobody knew its precise mechanism of action. They just knew that if you took it, you felt sleepy.”

The drug rose to prominence because patients could not overdose from it, an anomaly amongst sleeping pills at the time. It wasn’t until the early 60s when pregnant women who had taken thalidomide to help deal with morning sickness gave birth to babies with malformations. But in the 70s the drug was suspected to have other mechanisms.

In 1971 the concept of anti-angiogenesis was discovered which involves blocking the formation of new blood vessels necessary for a tumor to grow and survive.”Thalidomide was thought to be an anti-angiogenic drug. That is, it prevented the growth of new blood vessels.” That’s when thalidomide, and then lenalidomide, came to the forefront again. “The theory was that cancers can grow only until one millimeter in size, unless they are able to induce new blood vessels. And if they are not able to induce new blood vessel formation, the cancer will shrink and die,” Rajkumar explains. Lenalidomide gained approval for widespread use in multiple myeloma in the late-2000’s.

“I think finally now we understand how these drugs probably work.” says Rajkumar. Research has determined that Lenalidomide accelerates the breakdown of proteins in cancer cells critical to tumor growth and survival. By doing so, lenalidomide can increase the survival of patients with multiple myeloma by several years–a noble next chapter for a drug with fascinating beginnings.

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Dr. S. Vincent Rajkumar, MD is engaged in clinical, epidemiological and laboratory research in myeloma and related disorders. Read More