VISTA Frontline Trial - Most Common Side Effects (all grades)

Side Effect

Velcade-MP

Percentage of patients (N=340)

MP

Percentage of patients (N=337)

Thrombocytopenia

52%

47%

Neutropenia

49%

46%

Nausea

48%

28%

Peripheral neuropathy

47%

5%

Diarrhea

46%

17%

Anemia

43%

55%

Constipation

37%

16%

Neuralgia (nerve pain)

36%

1%

Low white blood cell count

33%

30%

Vomiting

33%

16%

Fever

29%

19%

Fatigue

29%

26%

Low lymphocyte count

24%

17%

Decreased appetite or weight loss

23%

10%

Weakness, malaise

21%

18%

Cough

21%

13%

Difficulty in sleeping

20%

13%

Swelling in the hands or feet

20%

10%

Toxicity

Dose modification or delay

If prolonged very serious (Grade 4) neutropenia or thrombocytopenia is experienced during a cycle, or thrombocytopenia with bleeding is observed in the previous cycle

Consider reduction of the melphalan dose by 25% in the next cycle

If platelet count is =30 x 10⁹/L or absolute neutrophil count (ANC) is =0.75 x 10⁹/L on a Velcade dosing day (other than day 1)

Velcade dose should be withheld

If several Velcade doses in consecutive cycles are withheld due to toxicity

Velcade dose should be reduced by one dose level (from 1.3 mg/m² to 1 mg/m², or from 1 mg/m² to 0.7 mg/m²)

Serious (Grade 3) or higher non-hematological toxicities

Velcade therapy should be withheld until symptoms of the toxicity have resolved to Grade 1 or baseline. Then, Velcade may be restarted with one dose level reduction (from 1.3 mg/m² to 1 mg/m², or from 1 mg/m² to 0.7 mg/m²).

For Velcade-related neuropathic pain and/or peripheral neuropathy, hold or modify Velcade as outlined here.

Severity of Peripheral Neuropathy Signs and Symptoms

Modification of Dose and Regimen

Grade 1* (paresthesias [sensations of numbness, tingling, or prickling], weakness, and/or loss of reflexes) without pain or loss of function

No action

Grade 1 with pain or Grade 2 (interfering with function but not with activities of daily living)

Reduce Velcade dose to 1.0 mg/m²

Grade 2 with pain or Grade 3 (interfering with activities of daily living)

Withhold Velcade therapy until toxicity resolves. When toxicity resolves, reinitiate with a reduced dose of Velcade at 0.7 mg/m² and change treatment schedule to once per week.

Grade 4 (permanent sensory loss that interferes with function, sensory neuropathy which is disabling, or motor neuropathy that is life threatening or leads to paralysis)

Discontinue Velcade

Modification of Velcade starting dose  

Mild

None Needed

None Needed

Moderate

First cycle: Reduce Velcade to 0.7 mg/m2 Subsequent cycles: Consider raising dose to 1.0 mg/m2 if tolerated well, or reducing dose further if necessary

Severe