Revlimid (lenalidomide) - Association with an Increased Risk of Second Cancers - For Health Professionals

Starting date:

May 1, 2012

Posting date:

May 3, 2012

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-170002639

This is duplicated text of a letter from Celgene Inc. Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on REVLIMID (lenalidomide)

May 1, 2012

Dear RevAid Registered Prescriber, RevAid^® Registered Pharmacist, or Allied Healthcare Professional:

Subject: Association of REVLIMID^® (lenalidomide) with an increased risk of second primary malignancies

Celgene Inc., in consultation with Health Canada, would like to inform you of important new safety information which has been added to the Product Monograph for REVLIMID^® (lenalidomide) capsules.

REVLIMID^® is an antineoplastic and immunomodulatory agent indicated for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities (approval was based on a surrogate marker of transfusion independence). REVLIMID^® is also indicated in combination with dexamethasone for the treatment of multiple myeloma (MM) in patients who have received at least one prior therapy.

The following points summarize the updated Product Monograph safety information:

• An increase of second primary malignancies (SPM) has been observed in clinical trials in previously treated multiple myeloma patients receiving lenalidomide and dexamethasone (3.98 per 100 patient-years) compared to controls (1.38 per 100 patient-years).
• In clinical trials of newly diagnosed multiple myeloma (not an authorized indication in Canada), a 4-fold increased incidence of SPM has been observed in patients receiving REVLIMID^®.
• The risk of occurrence of SPM must be taken into account before initiating treatment with REVLIMID^®. Physicians should carefully evaluate patients before and during treatment to screen for the occurrence of new malignancies.

The REVLIMID^® (lenalidomide) capsules Canadian Product Monograph was revised to include the following information under WARNINGS AND PRECAUTIONS:

An increase of second primary malignancies (SPM) has been observed in clinical trials in previously treated myeloma patients receiving lenalidomide/dexamethasone (3.98 per 100 patient-years) compared to controls (1.38 per 100 patient-years). Non invasive SPM comprise basal cell or squamous cell skin cancers. Most of the invasive SPMs were solid tumor malignancies.

In clinical trials of newly diagnosed multiple myeloma, a 4-fold increased incidence of second primary malignancies has been observed in patients receiving REVLIMID^® (7.0%) compared with controls (1.8%). Among invasive SPMs, cases of acute myeloid leukemia (AML), MDS and solid tumors were observed in patients receiving REVLIMID^® in combination with melphalan or immediately following high dose melphalan and autologous stem cell transplantation (ASCT); cases of B-cell malignancies (including Hodgkin's lymphoma) were observed in the clinical trials where patients received REVLIMID^® in the post ASCT setting.

The risk of occurrence of SPM must be taken into account before initiating treatment with REVLIMID^®.  Physicians should carefully evaluate patients before and during treatment using standard cancer screening for occurrence of second primary malignancies and institute treatment as required.

This warning was added as a result of a review conducted by Celgene in 2011 of all clinical trial data as well as spontaneous reports and comprehensive review of this data by Health Canada. A copy of the most up-to-date REVLIMID^® Product Monograph can be found in the Drug Product Database Online Query or on the  RevAid Web site.

Distribution restrictions:  REVLIMID^® is only available through a controlled distribution program called RevAid^®.  Under this program, only prescribers and pharmacists registered with the program are able to prescribe and dispense the product. In addition, REVLIMID^® can only be dispensed to patients who are registered and agree to comply with the requirements of the RevAid^® program. For more information, please log onto  RevAid.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of second primary malignancy or other serious or unexpected adverse reactions in patients receiving REVLIMID^® should be reported to Celgene Inc. or Health Canada.

To change your mailing address or fax number, contact:

Celgene Inc.
6755 Mississauga Road, Suite 600
Mississauga, ON
L5N 7Y2
Telephone: 1-877-923-5436
Facsimile:  1-289-291-4820
Email: drugsafety-canada@celgene.com

To report suspected adverse reactions to these or other health products, please contact Health Canada's Canada Vigilance Program toll-free at 1-866-234-2345, or visit the MedEffect^TM Canada Web site for information on how to report.

The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffect^TM Canada Web site in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.

For other health product inquiries related to this communication, please contact Health Canada at:
Marketed Health Products Directorate
E-mail: mhpd_dpsc.public@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

Sincerely,

original signed by

Dianne Azzarello, BSc. Phm
Senior Director, Pharmacovigilance & Regulatory Affairs