European myeloma experts recently developed guidelines for the appropriate management of side effects associated with novel agent therapy for older multiple myeloma patients. This article, Part 3 in a series, summarizes the guidelines for the management of Revlimid-related side effects. Part 1 describes the guidelines for the management of Velcade-related side effects, Part 2 summarizes the guidelines for thalidomide-related side effects, and Part 4 covers the European experts’ recommendations on novel agent use in specific patient populations.

Management Of Revlimid-Related Side Effects

Low Platelet Counts: 

Patients treated with Revlimid (lenalidomide) commonly experience low platelet counts. In newly diagnosed patients, between 7 percent and 8 percent experience severe to life-threatening low platelet counts. This rate increases to 15 percent for relapsed/refractory (resistant) patients.

The experts recommended that for patients taking Revlimid, a complete blood count, including platelet counts, should be performed at the start of treatment. Platelet counts should then be measured every week for the first eight weeks of therapy, followed by monthly measurements.

If platelets counts are below 75,000/μL on day 1 of a new cycle, patients should withhold treatment until platelet counts recover. At this time, treatment should be reinitiated at a lower dose.

If platelets counts are between 25,000/μL and 50,000/μL during a cycle, patients should not receive any anti-clotting treatment. Revlimid treatment should be reinitiated at a lower dose for the next cycle.

Low White Blood Cell Counts:

Patients treated with Revlimid also commonly experience low white blood cell counts.  Most patients experience the most severe cases of low white blood cell counts during early treatment cycles. As a result, the experts recommended that white blood cell counts are measured as part of a complete blood count at the start of treatment. After that, white blood cell counts should be measured biweekly if the counts are normal at the start of treatment.

If white blood cell counts are below 1,500/μL on day 1 of a new cycle, patients should withhold treatment until white blood cell counts recover. At this time, treatment should be reinitiated at a lower dose.

If white blood cell counts are below 500/μL during a cycle, then patients should begin treatment with granulocyte colony-stimulating factor (G-CSF) until white blood cell counts are at least 1,500/μL. At this time, treatment should be reinitiated at a lower dose.

If patients experience low white blood cell counts in combination with a fever, they should receive preventative antibiotic treatment. In addition, patients should seek medical attention within three hours.

Low Red Blood Cell Counts:

For patients with hemoglobin levels below 10 g/dL, the experts recommended the use of red blood cell-stimulating agents; however, the experts noted that these agents increase the risk of blood-clotting events, so they should be used with caution. If hemoglobin levels increase above 12 g/dL, they recommended that patients should discontinue use of red blood cell-stimulating agents.

Blood Clots:

As a single agent, Revlimid does not appear to increase the risk of formation of blood clots. However, when used in combination with melphalan (Alkeran) plus prednisone or dexamethasone (Decadron), the risk of blood-clotting events is significantly increased. In these cases, the experts recommended that patients receive preventative treatment with aspirin or heparin. In addition, the experts pointed out that according to previous research, treatment with low-dose dexamethasone lowers the risk of blood-clots, compared to high-dose dexamethasone.

Peripheral Neuropathy:

Peripheral neuropathy, a condition in which nerve damage in the extremities causes tingling or pain in the hands, arms, feet, or legs, is not a serious concern for patients treated with Revlimid. According to the study authors, about 2 percent of patients treated with Revlimid plus dexamethasone experience peripheral neuropathy.

Gastrointestinal Complications:

Gastrointestinal complications, such as nausea, vomiting, diarrhea, or constipation, are frequently observed in patients receiving treatment with Revlimid. The experts recommended the use of anti-vomiting drugs, anti-diarrhea drugs, and laxatives to manage those complications. According to the experts, dose reductions or treatment interruptions are rarely necessary.

Cardiovascular Disorders:

Patients treated with Revlimid have an increased risk for heart attacks, especially those with pre-existing risk factors. The experts recommended that the patients should be closely monitored and that they stop smoking and use blood pressure and cholesterol medications as needed.

Skin Reactions:

Patients treated with Revlimid may experience skin reactions. The experts pointed out that skin reactions may resolve by interrupting treatment. However, in severe cases, they advised that patients should permanently discontinue Revlimid treatment.

For more information, please refer to the original study in the journal Blood Reviews (abstract).