FDA Issues Extensive Update About Revlimid And Second Cancers
Published: May 7, 2012 8:15 pm; Updated: May 9, 2012 10:30 am
The U.S. Food and Drug Administration earlier today issued an extensive update regarding the risk of developing a second cancer while being treated with Revlimid.
The update comes on the heels of a change the Food and Drug Administration (FDA) made to the prescribing information for Revlimid (lenalidomide) in March of this year.
The change involved the addition of a warning that patients being treated with Revlimid have an increased risk of developing a second cancer (see related Beacon news).
Today’s update by the FDA includes more specific details of the agency's analyses of Revlimid and second cancers.
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In the update, the FDA says that it continues to recommend that physicians monitor patients being treated with Revlimid for the development of second cancers, and that physicians take into account both the potential benefit of the drug and the risk of second cancers when they consider treating a patient with Revlimid.
The FDA also urges patients to contact their health care professional if they have any questions or concerns about Revlimid.
Revlimid is marketed by the U.S. pharmaceutical company Celgene (NASDAQ: CELG). Representatives from Celgene did not respond to requests for comment on today's FDA update.
The new Food and Drug Administration’s analyses show that newly diagnosed multiple myeloma patients treated with Revlimid maintenance therapy after stem cell transplantation are three times more likely to develop a second cancer than patients who do not receive Revlimid maintenance.
Data from three ongoing clinical trials show so far that 7.9 percent of newly diagnosed patients receiving Revlimid maintenance have developed a second cancer, compared to 2.8 percent of patient who received a placebo. Patients receiving Revlimid were more likely to develop acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin’s lymphoma. The median time from start of Revlimid treatment till diagnosis of a second cancer was two years.
The analyses also show that relapsed and refractory myeloma patients treated with Revlimid and dexamethasone (Decadron) are more likely to develop a second cancer than patients treated with dexamethasone alone.
Specifically, data from the two clinical trials that supported the FDA’s approval of Revlimid show that 3.98 percent of relapsed and refractory myeloma patients developed a second cancer during each year of treatment with Revlimid and dexamethasone, compared to 1.38 percent of patients treated with dexamethasone and placebo. A key contributor to the different rates of second cancer was a noticeably higher rate of non-melanoma skin cancer among the patients treated with Revlimid.
However, when FDA adjusted its analysis of non-melanoma skin cancer rates to account for differences in how long patients were observed on treatment during the clinical trials, it found that 1.71 percent of Revlimid-treated patients developed a non-melanoma skin cancer per year of treatment, as compared to 0.91 percent of patients who did not receive Revlimid. The FDA stated that these two rates are statistically similar.
The FDA also suggested in today's update that the prescribing information for Revlimid has been further updated to reflect the agency's newly released analyses. The Beacon has not been able to confirm with either the FDA or Celgene whether or not this actually is the case, and there is no evidence on the FDA's website of newly revised prescribing information for Revlimid. (See important update below.)
Today's FDA update follows an announcement last week by regulators in Ottawa that information about the risk of secondary cancer has been added to Revlimid’s Canadian prescribing information (see the related Health Canada announcement).
European regulators concluded their review of Revlimid and second cancers last September by reporting that “the benefits of Revlimid, particularly improved survival, continue to outweigh the risks” (see related Beacon news).
At the same time, the regulators moved to include in Revlimid's European prescribing information language about second cancers that is more detailed than what has been included thus far in the drug's U.S. and Canadian prescribing information.
The current European prescribing information for Revlimid, for example, states that "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%)."
For further coverage of developments related to Revlimid and second cancers, please see the compilation of Beacon articles about relevant research findings and announcements.
The full text of today’s FDA update can be found at the FDA website. The key parts of the statement are included below for the convenience of the Beacon’s readers.
Update (May 9, 2012; 10:30 a.m.): A spokesperson for the FDA has informed The Beacon that the agency is not currently planning additional revisions to Revlimid’s prescribing information beyond those made public by the FDA in March. Thus, the Revlimid prescribing information currently available on the FDA website is up to date.
The spokesperson further clarified that the FDA update discussed in the Beacon article above was intended, in part, to explain the agency’s rationale for the changes to Revlimid’s prescribing information published on the FDA website in March.
Key Text of FDA Drug Safety Communication:
Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies
The U.S. Food and Drug Administration (FDA) is informing the public of an increased risk of second primary malignancies (new types of cancer) in patients with newly-diagnosed multiple myeloma who received Revlimid (lenalidomide). Clinical trials conducted after Revlimid was approved showed that newly-diagnosed patients treated with Revlimid had an increased risk of developing second primary malignancies compared to similar patients who received a placebo. Specifically, these trials showed there was an increased risk of developing acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma.
This safety information has been added to the Warnings and Precautions section of the Revlimid drug label. The patient Medication Guide is also being updated to inform patients about this risk.
Healthcare professionals should consider both the potential benefit of Revlimid and the risk of second primary malignancies when deciding to treat patients with this drug, and monitor patients for this risk.
Patients should contact their healthcare professional if they have any questions or concerns about Revlimid …
FDA reviewed controlled clinical trials of Revlimid as maintenance therapy in patients with newly-diagnosed multiple myeloma and for the treatment of relapsed/refractory multiple myeloma, to evaluate the risk of developing a second primary malignancy with Revlimid.
Second primary malignancies in patients with newly diagnosed multiple myeloma
In three prospective, randomized trials, patients with newly-diagnosed multiple myeloma received initial chemotherapy or chemotherapy plus blood stem cell transplantation followed by treatment with Revlimid or a placebo. This treatment protocol was used to study the effect of Revlimid as maintenance therapy. A pooled analysis of the three ongoing trials, as of February 28, 2011, showed 65 second primary malignancies among 824 patients in the Revlimid treatment arms compared to 19 second primary malignancies among 665 patients in the treatment arms that did not include Revlimid maintenance (7.9% vs. 2.8%; p<0.001). This difference is almost a three-fold increase in new malignancies for the groups receiving Revlimid versus the groups that did not receive Revlimid. The second primary malignancies noted included acute myelogenous leukemia (AML), myelodysplastic syndromes (MDS), and B-cell malignancies. Overall, 30 (3.6%) second primary hematologic malignancies were reported in the Revlimid treatment arms (22 MDS/AML, 5 Hodgkin lymphoma, 3 B-cell acute lymphoblastic leukemia) compared with 2 (0.3%) cases of AML in the study arms not receiving Revlimid. The median time from start of Revlimid to a diagnosis of a second primary malignancy was two years. Based on the available data, there appears to be no difference in the incidence of non-melanoma skin cancers or of solid tumors between the patients who received Revlimid and those who did not.
Second primary malignancies in patients with relapsed/refractory multiple myeloma
A retrospective pooled analysis of second primary malignancies also was conducted on data derived from the two clinical trials that supported the initial FDA approval for relapsed multiple myeloma. These were multicenter, double-blind, placebo-controlled, parallel-group trials of Revlimid plus high-dose dexamethasone therapy versus dexamethasone alone in the treatment of patients with relapsed or refractory multiple myeloma. The incidence rates of developing a second primary malignancy during the treatment phase of these trials were 3.98 and 1.38 per 100 person-years for patients in the Revlimid / dexamethasone and the placebo / dexamethasone groups, respectively. The higher incidence rate of second primary malignancies in the Revlimid / dexamethasone group was largely accounted for by the higher incidence of non-melanoma skin cancers with Revlimid (2.4 vs. 0.91 per 100 person-years for the Revlimid / dexamethasone and placebo / dexamethasone groups, respectively). The patients in the Revlimid / dexamethasone group had longer on-study treatment time compared to the placebo / dexamethasone group (467 person-years vs. 218.7 person-years, respectively). When adjusted for the differences in observation time on-study, the incidence rate of invasive non-melanoma skin cancers was not substantially different between the two groups (1.71 vs. 0.91 per 100 person-years, respectively).
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- FDA Announces Investigation Into Revlimid, Thalidomide, And Secondary Cancers
- Beacon BreakingNews – Updated Data On Revlimid Maintenance And Second Cancers Presented At IMW
- Revlimid Maintenance And Secondary Cancers In Myeloma Patients: More Details Emerge
- Questions & Answers About The FDA’s Investigation Into The Safety of Revlimid And Thalidomide