What are the common side effects of Velcade (bortezomib)?

Velcade (Bortezomib) Side Effects

The most clinically significant side effects of Velcade are peripheral neuropathy (occurring in 35-47% of patients) and thrombocytopenia (occurring in 33% of patients), with gastrointestinal symptoms (nausea 52%, diarrhea 52%) being the most common overall adverse effects. 1

Hematologic Toxicities

• Thrombocytopenia occurs in approximately 33% of patients overall, with Grade 3/4 severity in 4% of cases 1
• Neutropenia presents as Grade 3/4 in up to 58% of patients in certain regimens (MPL combination) 2
• Severe thrombocytopenia occurs in approximately 5% or less of patients in the frontline setting 2
• These hematologic effects are generally manageable and predictable with appropriate monitoring 2

Peripheral Neuropathy (Most Important Non-Hematologic Toxicity)

• Peripheral neuropathy is the key dose-limiting toxicity and occurs in 35-47% of patients, with Grade 3/4 severity in 8-13% 2, 1
• The neuropathy is predominantly sensory (90% of cases), though motor neuropathy occurs in 10% of cases 2
• Neuropathic pain in fingertips and toes is a major distinguishing feature compared to thalidomide-induced neuropathy 2
• Grade 2 peripheral neuropathy occurs in 20.5% and Grade 3-4 in 9.2% during induction therapy 2

Risk Factors and Mitigation Strategies

• Major risk factors include cumulative dose and treatment schedule (twice-weekly dosing) 2
• Weekly dosing reduces Grade 3/4 neuropathy to 6-7% while maintaining efficacy, compared to twice-weekly schedules 2
• Subcutaneous administration is preferred over intravenous route as it significantly reduces peripheral neuropathy rates 2
• Approximately 70% of patients experience partial or complete reversibility of neurologic symptoms with early recognition, dose reduction, or discontinuation 2

Gastrointestinal Toxicities

• Nausea occurs in 52% of patients 1
• Diarrhea occurs in 52% of patients, with Grade 3 severity in 26% in some combination regimens 2
• Vomiting occurs in 29% of patients 1
• Constipation occurs in 30% of patients 1
• Anorexia occurs in 19-21% of patients 1

General Constitutional Symptoms

• Fatigue occurs in 25-39% of patients, with Grade 3/4 severity in 6% 1
• Asthenia (weakness) occurs in 16% of patients, with Grade 3/4 severity in 5% 1
• Pyrexia (fever) occurs in 16% of patients 1

Infectious Complications

• Herpes zoster reactivation occurs in 11% of patients, with Grade 3/4 severity in 3% 1
• Prophylactic acyclovir is recommended to reduce the incidence of bortezomib-associated herpes zoster 2

Rare but Serious Toxicities

• Cardiac toxicity: cardiogenic shock, congestive heart failure, and cardiac arrest have been reported as bortezomib-related deaths 1
• Pulmonary toxicity: respiratory insufficiency has been reported 1
• Motor neuropathy: though rare, can be severely debilitating and may require steroids or intravenous immunoglobulin for treatment 3
• Skin rash occurs in 11% of patients, though severe cutaneous manifestations are rare 1, 4

Important Clinical Considerations

• Bortezomib has low risk of deep vein thrombosis compared to immunomodulatory agents, eliminating the need for routine anticoagulation prophylaxis 2
• Bortezomib-based regimens may be valuable in patients with renal failure and those with adverse cytogenetic features 2
• Adverse events are predictable and manageable with patient monitoring and appropriate supportive care 2
• The overall toxicity profile has improved dramatically with subcutaneous administration and implementation of early recognition guidelines 5