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 1 in a series, summarizes the guidelines for the management of Velcade-related side effects. Part 2 summarizes the European experts’ guidelines for the management of thalidomide-related side effects, Part 3 summarizes the guidelines for the management of Revlimid-related side effects, and Part 4 summarizes recommendations on novel agent use in specific patient populations.

The novel agents Velcade (bortezomib), thalidomide (Thalomid), and Revlimid (lenalidomide) have been integrated into the treatment of both younger and older multiple myeloma patients over the last couple of years.

However, according the European myeloma experts, older patients don’t tolerate the treatment-associated side effects as well as younger patients, which may lead to a lower treatment adherence among older patients.

They pointed out that due to increased side effects of the novel agents, in particular in combination with other drugs, it is critical that older patients are closely monitored and any emerging side effects are immediately and properly managed.

The experts therefore developed the following guidelines for the management of side effects in older myeloma patients.

Management Of Velcade-Related Side Effects

Low Platelet Counts:

Patients treated with Velcade commonly experience low platelet counts and low white blood cell counts. According to the authors of the guidelines, these complications affect between 35 percent and 52 percent of patients treated with single-agent Velcade and between 19 percent and 49 percent of patients treated with Velcade-based combination therapies.

The experts recommended that in patients experiencing low platelet counts, the counts should be regularly monitored. In general, platelet counts should initially be measured at the beginning of each treatment cycle and then after every other Velcade dose.

If a patient is receiving Velcade in combination with an alkylating agent, such as melphalan (Alkeran) or cyclophosphamide (Cytoxan), then it is recommended that the patient only undergo treatment if platelet counts are at least 70,000/μL on day 1 of each cycle. Patients may initiate treatment at a lower dose when platelet counts increase to the required level.

If a patient is receiving single-agent Velcade or Velcade in combination with non-alkylating agents, then it is recommended that the patient only undergo treatment if platelet counts are at least 25,000/μL on day 1 of each cycle. Patients may initiate treatment at a lower dose when platelet counts increase to at least 50,000/μL.

If platelets counts are below 30,000/μL on any dosing day after day 1, then patients should withhold treatment until platelet counts increase to at least 50,000/μL. At this time, treatment would be reinitiated at a lower dose.

Low White Blood Cell Counts:

For patients experiencing low white blood cell counts, it is recommended that they take granulocyte colony-stimulating factor (G-CSF) as a primary or secondary preventative treatment to reduce the severity of the side effect.

If a patient is receiving Velcade in combination with an alkylating agent, then it is recommended that the patient only undergo treatment if white blood cell counts are at least 1,000/μL on day 1 of each cycle. Patients may initiate treatment at a lower dose when white blood cell counts have recovered. Patients receiving melphalan may also need to reduce the melphalan dosage.

If a patient has white blood cell counts less than 500/μL on day 1 of each cycle, despite use of G-CSF, patients may initiate treatment at a lower dose only when white blood cell counts are at least 1,000/μL. Patients receiving melphalan may also need to reduce the melphalan dosage.

If white blood cell counts are below 750/μL (in combination with alkylating agents) or below 500/μL (for other combinations) on any dosing day after day 1, patients should withhold treatment until white blood cell counts recover. At this time, treatment should be reinitiated at a lower dose.

Low Red Blood Cell Counts:

Patients with hemoglobin levels below 10 g/dL should receive treatment with red blood cell-stimulating agents. There is no need to modify Velcade dosage.

Blood Clots:

Venous thromboembolism is a condition in which a blood clot forms in a vein. This complication may be extremely serious, as a piece of the clot can break off, travel through the vein, and block an artery to the lungs.

Velcade does not appear to increase the risk of formation of blood clots. In fact, when used in combination with thalidomide or Revlimid, it may even protect against the formation of blood clots. If patients have already experienced a blood-clot or are simultaneously taking thalidomide or Revlimid, it is recommended that patients receive preventative treatment with either aspirin or heparin.

Peripheral Neuropathy:

Peripheral neuropathy is a serious and sometimes debilitating condition in which nerve damage in the extremities causes tingling or pain in the hands, arms, feet, or legs. Between 31 percent and 47 percent of patients treated with Velcade experience peripheral neuropathy. According to the experts, most cases are of mild or moderate severity with Velcade treatment.

The experts recommended that patients should be carefully monitored for neurotoxic symptoms before and during treatment. Symptoms typically emerge during the first two to four months of treatment. Once symptoms occur, the experts suggested that the Velcade dose be lowered to manage the complication.

Gastrointestinal Complications:

Patients experiencing gastrointestinal complications, such as nausea, vomiting, diarrhea, or constipation, are advised to increase their fluid intake. If needed, patients may also take anti-diarrhea drugs or anti-vomiting drugs. Patients experiencing constipation should adhere to a high-fiber diet and may use stool softeners or laxatives as needed. In more serious cases, Velcade dosage should be reduced or treatment may be withheld until the complication is properly managed.

Infection:

Patients treated with Velcade have an increased risk of reactivating the varicella zoster virus, which leads to shingles. As a result, the experts recommended that all patients treated with Velcade receive antiviral preventative treatment.

When Velcade is given as part of a combination treatment, the experts pointed out that the greatest risk of infection is during the first three months of treatment. They suggested that patients receive preventative antibiotics during that time.

Skin Reactions:

For patients treated with Velcade, as many as 20 percent may experience a rash. Patients may treat the rash with topical medications, such as hydrocortisone. In severe cases, patients may take low-dose oral prednisone.

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