Lenalidomide (Revlimid)

General information

Class/mechanism: Second-generation immunomodulatory drug (IMiD) similar to Thalidomide (Thalomid); mechanism not fully understood. Lenalidomide's mechanism may involve immunomodulatory, antiinflammatory, and antiangiogenic effects and suppression of tumor necrosis factor-alpha (TNF-α) from peripheral blood mononuclear cells. It has been observed to inhibit cells with the 5q deletion in myelodysplastic syndromes. It has also been seen in vitro to inhibit cyclooxygenase-2 (COX-2) expression, but not COX-1.
Route: PO
Extravasation: n/a

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, UpToDate (courtesy of Lexicomp), or the prescribing information.

Toxicity management

• Use of Lenalidomide (Revlimid) requires participation the Revlimid REMS program.

Thrombosis

• 2006 (two simultaneously published NEJM letters to the editor): link to original article PubMed link to letter #1 PubMed link to letter #2
• 2011: Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. link to original article PubMed

Diseases for which it is established (work in progress)

• Multiple myeloma
• Myelodysplastic syndrome
• Non-Hodgkin lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Marginal zone lymphoma

Diseases for which it is used

• Adult T-cell leukemia-lymphoma
• B-cell lymphoma of mucosa-associated lymphoid tissue
• Chronic lymphocytic leukemia
• Chronic myelomonocytic leukemia
• Cutaneous T-cell lymphoma
• Diffuse large B-cell lymphoma
• Classical Hodgkin lymphoma
• Light-chain (AL) amyloidosis
• Myelofibrosis
• Peripheral T-cell lymphoma
• Plasma cell leukemia
• POEMS syndrome
• Polycythemia vera
• Smoldering multiple myeloma
• Transformed lymphoma
• Waldenström macroglobulinemia

Patient drug information

• Lenalidomide (Revlimid) package insert
• Lenalidomide (Revlimid) patient medication guide
• Lenalidomide (Revlimid) patient drug information (Chemocare)
• Lenalidomide (Revlimid) patient drug information (UpToDate)

History of changes in FDA indication

Follicular lymphoma; Marginal zone lymphoma

• 2019-05-28: Approved in combination with a rituximab product for previously treated follicular lymphoma (FL) and previously treated marginal zone lymphoma (MZL). (New disease entity; based on AUGMENT and MAGNIFY)

Mantle cell lymphoma

• 2013-06-05: Approved for patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. (New disease entity; based on EMERGE)

Multiple myeloma

• 2006-06-29: Approved for treatment of patients with multiple myeloma (MM), in combination with dexamethasone, in patients who have received at least one prior therapy.] (New disease entity; based on MM-009 and MM-010)
• 2015-02-17: Approved for multiple myeloma (MM), in combination with dexamethasone. (Prior treatment requirement removed; based on FIRST_MM)
• 2017-02-22: Approval expanded as maintenance therapy for patients with multiple myeloma following autologous stem cell transplant. (Approval expanded to maintenance therapy after upfront treatment; based on CALGB 100104 and IFM 2005-02)

Myelodysplastic syndrome

• 2005-12-28: Approved for patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities. (Initial approval; based on CC-5013-MDS-003)

History of changes in EMA indication

• 2007-06-14: Initial authorization

History of changes in Health Canada indication

• 2008-01-17: Initial notice of compliance with conditions
• 2013-06-06: Conditions were met

History of changes in PMDA indication

• 2010-06-25: Initial approval for the treatment of relapsed or refractory multiple myeloma.
• 2010-08-20: New additional indication and a new dosage for the treatment of myelodysplastic syndrome associated with a deletion 5q cytogenetic abnormality.
• 2015-12-21: revised indication for the treatment of multiple myeloma.
• 2017-03-02: New additional indication and a new dosage for the treatment of relapsed or refractory adult T-cell leukemia/lymphoma.
• 2020-02-21: New indications and a new dosage for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma.

Also known as

• Code names: CC-5013, IMiD-1, NSC-703813
• Brand names: Adlinod, Immunomide, Kabillon, Lenalid, Lenalidomid, Lenangio, Lenmid, Lenome, Lenomust, Lenzest, Lidmed, Linamide, Lynide, MyeloSar, Revlimid