Bortezomib (Velcade)

General information

Class/mechanism: Reversible inhibitor of the 26S proteasome, interfering with degradation of ubiquitinated proteins. This disrupts normal homeostatic mechansims, leading to cell death.
Route: IV, SC
Extravasation: irritant

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, Medscape, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established (work in progress)

• Follicular lymphoma
• Mantle cell lymphoma
• Multiple myeloma

Diseases for which it is used

• B-cell lymphoma of mucosa-associated lymphoid tissue
• Castleman disease
• Light-chain (AL) amyloidosis
• Peripheral T-cell lymphoma
• Plasma cell leukemia
• Waldenström macroglobulinemia

Diseases for which it was used

• Diffuse large B-cell lymphoma

Notable side effects

• HSV reactivation
  • Use antiviral prophylaxis (such as with acyclovir (Zovirax) 400 mg PO once per day or valacyclovir (Valtrex) 250 to 500 mg PO once per day) to decrease risk of reactivating herpes zoster in patients treated with bortezomib
• Neuropathy

Patient drug information

• Bortezomib (Velcade) patient drug information (Chemocare)
• Patient counseling information can be found in the package insert
• Bortezomib (Velcade) patient drug information (UpToDate)

History of changes in FDA indication

Mantle cell lymphoma

• 2006-12-08: Approved for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. (New disease entity; based on PINNACLE)
• 2014-10-08: Approved for treatment of patients with mantle cell lymphoma. (including first-line therapy for untreated patients; previously was only approved for patients who had received at least one prior treatment; based on LYM-3002)

Multiple myeloma

• 2003-05-13: Initial accelerated approval for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. (Based on SUMMIT)
• 2005-03-25: Converted to regular approval for the treatment of multiple myeloma patients who have received at least 1 prior therapy. (Based on APEX)
• 2008-06-23: Approved for the treatment of patients with multiple myeloma. (previously was only approved for patients who had received prior therapy; based on VISTA)
• 2012-01-23: Approved for subcutaneous administration of patients with multiple myeloma. (Based on MMY-3021)
• 2014-08-11: Approved for retreatment of patients with multiple myeloma. (Based on RETRIEVE)

History of changes in EMA indication

• 2004-04-26: Initial marketing authorization as Velcade.
• 2013-07-31: Velcade in combination with dexamethasone is indicated for the induction treatment of adult patients with previously untreated multiple myeloma who are eligible for high dose chemotherapy with haematopoietic stem cell transplantation.
• 2013-07-31: Velcade in combination with dexamethasone and thalidomide is indicated for the induction treatment of adult patients with previously untreated multiple myeloma who are eligible for high dose chemotherapy with haematopoietic stem cell transplantation.
• 2013-12-18: Extension of indication for Velcade in combination with pegylated liposomal doxorubicin in patients with relapsed and /or progressive multiple myeloma who have received at least 1 prior therapy.
• 2013-12-18: Extension of indication for Velcade in combination with dexamethasone in patients with relapsed and /or progressive multiple myeloma who have received at least 1 prior therapy.
• 2015-01-30: Extension of indication for the use of VELCADE in combination with rituximab, cyclophosphamide, doxorubicin and prednisone for the treatment of adult patients with previously untreated mantle cell lymphoma.
• Uncertain date: Velcade as monotherapy is indicated for the treatment of adult patients with progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for haematopoietic stem cell transplantation.
• Uncertain date: Velcade in combination with pegylated liposomal doxorubicin is indicated for the treatment of adult patients with progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for haematopoietic stem cell transplantation.
• Uncertain date: Velcade in combination with dexamethasone is indicated for the treatment of adult patients with progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for haematopoietic stem cell transplantation.
• Uncertain date: Velcade in combination with melphalan and prednisone is indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for high dose chemotherapy with haematopoietic stem cell transplantation.
• Uncertain date: Velcade in combination with rituximab, cyclophosphamide, doxorubicin and prednisone is indicated for the treatment of adult patients with previously untreated mantle cell lymphoma who are unsuitable for haematopoietic stem cell transplantation.

History of changes in Health Canada indication

• 2005-01-27: Initial notice of compliance with conditions
• 2007-09-11: Conditions were met

History of changes in PMDA indication

• 2006-10-20: Initial approval for treatment of relapsed or refractory multiple myeloma.
• 2011-09-16: New indication and a new dosage for the treatment of multiple myeloma.
• 2012-12-21: New route of administration indicated for the treatment of multiple myeloma.
• 2015-06-26: New additional indication and a new dosage for the treatment of patients with mantle cell lymphoma.
• 2018-03-23: New additional indication and a new dosage indicated for the treatment of Waldenström's macroglobulinemia and lymphoplasmacytic lymphoma.
• 2021-08-25: New indication and a new dosage for the treatment of systemic AL amyloidosis.

Also known as

• Code names: LDP-341, MLN-341, PS-341
• Brand names: Biocure, Borater, Bortecad, Bortemib, Bortenat, Bortetrust, Bortrac, Borvex, Borviz, Botepar, Bromadene, Egybort, Mibor, Myezom, Norvelzo, Ortez, Velcade, Zomib, Zuricade