New drugs join guidelines for multiple myeloma

January 22, 2007

Multiple myeloma (MM) is not curable, according to the Multiple Myeloma Research Foundation (MMRF), but it is treatable. The MM panel of the National Comprehensive Cancer Network (NCCN) has added several drugs and drug combinations to the MM guidelines. Bortezomib (Velcade, Millennium Pharmaceuticals and Johnson & Johnson), lenalidomide (Revlimid, Celgene), and melphalan (Alkeran, GlaxoSmithKline) are all included in several combinations with cortico-steroids and other chemotherapy drugs. Lenalidomide is also recommended as single-agent treatment for salvage therapy.

Multiple myeloma is the second most common form of hematologic cancer (non-Hodgkin's lymphoma is the first), according to MMRF. The disease occurs in plasma cells, which are responsible for producing immune globulins (antibodies). Myeloma causes an overproduction of abnormal plasma cells. When these abnormal cells collect in more than one bone, the disease is termed multiple myeloma.

The addition of new drugs with new mechanisms of action is significant, said Dixie Esseltine, M.D., VP of global medical affairs for Millennium Pharmaceuticals. "The goal in developing combinations is to put the most active drugs together."

Bortezomib is the first in a new class of drugs called proteasome inhibitors. According to nonclinical research gained so far, certain proteins within cells are tagged with ubiquitin and then degraded by proteasomes. Disrupting this process with proteasome inhibitors can lead to the death of cancer cells. Research suggests that proteasome inhibitors may also make the bone marrow less hospitable to myeloma cells and decrease the ability of those cells to adhere to other cells in the bone marrow.

Lenalidomide is an analog of thalidomide. Clinical studies have provided evidence that lenalidomide is effective against MM. One well-known participant in one of these studies was Geraldine Ferraro, former Congresswoman from New York and vice-presidential candidate. In 2001, Ferraro testified at a congressional hearing to raise awareness of MM, argue for additional research funding, and urge the FDA to speed drug approvals.

The FDA has since approved lenalidomide, in combination with dexamethasone, for MM patients who have tried at least one other treatment. Now, NCCN has added the drug to the list of recommended drug regimens for MM.

Because lenalidomide is so closely related to thalidomide, it carries the same contraindications and warnings as thalidomide. Birth defects, clotting, neutropenia, and throm- bocytopenia are primary concerns. The potential toxicities are so serious that lenalidomide is in a restricted distribution program similar to the one used for thalidomide. Physicians and pharmacies cannot prescribe or dispense lenalidomide without first registering or contracting with Celgene's RevAssist program. Patients cannot receive the drug unless they enroll in and comply with the RevAssist program.

Thousands of Americans are diagnosed with MM each year, and there are currently about 50,000 Americans living with the disease, according to MMRF. However, with all of the treatments now available for MM, people with the disease are healthier and living longer.

THE AUTHOR is a clinical writer based in the Seattle area.