The U.S. Food and Drug Administration has added a warning to the prescribing information for Revlimid stating that patients being treated with the drug have an increased risk of developing a second cancer.
The warning has been added in two parts of the prescribing information.
In the upfront ‘Warnings and Precautions’ section, text has been included stating that “Higher incidences of SPM [second primary malignancies] were observed in controlled trials of patients with multiple myeloma receiving Revlimid.”
Later in the document, the warning is expanded to explain that studies have shown that multiple myeloma patients treated with Revlimid
(lenalidomide) as well as melphalan
(Alkeran) and stem cell transplantation were more likely to develop a second cancer than those receiving comparable treatment without Revlimid. In particular, the Revlimid-treated patients were at higher risk of developing acute myelogenous leukemia and Hodgkin’s lymphoma.
The Food and Drug Administration (FDA) recommends in the prescribing information that physicians monitor patients being treated with Revlimid for the development of second cancers and take into account both the potential benefit of the drug and the risk of second cancers when considering treatment with Revlimid.
Revlimid is marketed by the U.S. pharmaceutical company Celgene (NASDAQ: CELG).
Concerns about a potential Revlimid-secondary cancer link first emerged at the American Society of Hematology annual meeting in December 2010, when results were presented from three trials that showed higher rates of reported second cancers among myeloma patients treated long-term with Revlimid therapy compared to other patients in the same studies.
Despite extensive follow-up research and investigation, concerns about Revlimid and secondary cancer persist. They are reflected, for example, in the recent International Myeloma Working Group consensus statement on maintenance therapy, which cites the risk of secondary cancer in its discussion of maintenance therapy with Revlimid (see related Beacon
The recent change in the U.S prescribing information for Revlimid was preceded earlier this year by a change in the European prescribing information for the drug. The European change reflects the results of a safety review by the European Medicines Agency, which was concluded last September (see related Beacon
The warning added to the European prescribing information is more extensive than the warning added by the FDA. In particular, the European agency added three paragraphs to the section on “other special warnings and precautions for use.”
The first two paragraphs note that, in both previously treated as well as newly diagnosed multiple myeloma patients, treatment with Revlimid has been associated with a three- to four-fold increase in the rate of second cancers versus what was observed in the trial control groups.
The third paragraph then states, “The risk of occurrence of [second cancers] 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 indicated.”
The U.S. Food and Drug Administration began its own safety investigation of Revlimid – and alsothalidomide
(Thalomid), which is chemically similar to Revlimid – in April 2011. An FDA representative contacted by The Beacon was unable at this time to clarify whether the recent change in Revlimid’s prescribing information reflects the conclusion of the agency’s investigation.
Neither the FDA nor European authorities have thus far made any changes to the prescribing information for Thalomid related to secondary cancers.
At the 2011 American Society of Hematology meeting this past December, Dr. Antonio Palumbo of the University of Torino in Italy summarized results of a retrospective analysis of the risk of secondary cancer associated with Revlimid and thalidomide treatment (see related Beacon
The results of the analysis indicate that treatment with Revlimid in and of itself may not increase the risk of secondary cancers.
Instead, there may be an interaction between treatment with melphalan and treatment with Revlimid (or thalidomide) that increases a patient’s risk of developing secondary cancers.
Dr. Palumbo also presented data showing that the risk of developing secondary cancers when treated with Revlimid is generally lower than the risk of a number of serious side effects that can occur during common myeloma treatment regimens.
Addition To The U.S. Prescribing Information For Revlimid
Second Primary Malignancies (SPM): Higher incidences of SPM were observed in controlled trials of patients with multiple myeloma receiving Revlimid.
Patients with multiple myeloma treated with lenalidomide [Revlimid] in studies including melphalan and stem cell transplantation had a higher incidence of second primary malignancies, particularly acute myelogenous leukemia (AML) and Hodgkin lymphoma, compared to patients in the control arms who received similar therapy but did not receive lenalidomide. Monitor patients for the development of second malignancies. Take into account both the potential benefit of lenalidomide and the risk of second primary malignancies when considering treatment with lenalidomide.
Addition To The European Prescribing Information For Revlimid
An increase of second primary malignancies (SPM) has been observed in clinical trials in previously treated myeloma patients receiving lenalidomide [Revlimid] / 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 tumour 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 AML [acute myeloid leukemia], MDS [myelodysplastic syndromes] and solid tumours were observed in patients receiving Revlimid in combination with melphalan or immediately following high dose melphalan and ASCT [autologous stem cell transplant]; cases of B-cell malignancies (including Hodgkin’s lymphoma) were observed in the clinical trials where patients received Revlimid in the post ASCT setting.