Preview Newsletter
Research MM
-
Celgene Receives Positive Opinion From EU For Revlimid After Article 20 Review
Sep 23, 2011 | RTT News
Celgene International Sàrl, the international arm of biopharmaceutical company Celgene Corp. (CELG), on Friday said further to the Article 20 review, its cancer drug Revlimid received a positive opinion from the European regulators for use in combination with dexamethasone for treatment of multiple myeloma patients who have undergone at least one prior therapy. -
Safety Concerns Force Withdrawal Of Revlimid Application For Expanded Use In Europe
Jun 21, 2012 | The Myeloma Beacon
Celgene, the company that markets Revlimid in the United States and internationally, announced this morning that it has withdrawn its application in Europe to have the drug approved for use as initial therapy for newly diagnosed myeloma patients as well as for maintenance therapy. -
FDA Drug Safety Communication: Ongoing safety review of Revlimid (lenalidomide) and possible increased risk of developing new malignancies
Aug 4, 2011 | FDA
The U.S. Food and Drug Administration (FDA) is informing the public that we are aware of results from clinical trials conducted inside and outside the United States that found that patients treated with Revlimid (lenalidomide) may be at an increased risk of developing new types of cancer compared to patients who did not take the drug. -
FDA Drug Safety Communication: Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies
May 7, 2012 | FDA
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. -
FDA: Revlimid Linked to Second Cancers
May 8, 2012 | MedPage Today
By Michael Smith
Treatment of multiple myeloma with lenalidomide (Revlimid) as maintenance therapy is associated with an increased risk of second primary cancers, the FDA warned. -
FDA Issues Extensive Update About Revlimid And Second Cancers
May 7, 2012 | The Myeloma Beacon
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.
Article 20 Review
Second Primary Malignancies
-
Celgene Receives Positive Opinion From EU For Revlimid After Article 20 Review
Sep 23, 2011 | RTT News
Celgene International Sàrl, the international arm of biopharmaceutical company Celgene Corp. (CELG), on Friday said further to the Article 20 review, its cancer drug Revlimid received a positive opinion from the European regulators for use in combination with dexamethasone for treatment of multiple myeloma patients who have undergone at least one prior therapy.
The company said it got the notification today that the E.U. Committee for Medicinal Products for Human Use or CHMP, on behalf of the European Medicines Agency or EMA, has concluded an Article 20 review of the drug.
The Article 20 Review was initiated following reports of incidence of second primary malignancies or SPM in clinical studies. Such reviews are mandatory by which the European Commission can conduct a reassessment of the benefit-risk of a centrally authorized product in an approved indication within the EU.
CHMP now concluded that the drug demonstrates a positive benefit-risk profile, and also recommended to update the drug's product information to include information on SPMs.
With this, Celgene noted the conclusion of the Article 20 review of clinical data in the approved indication for Revlimid, including pivotal studies MM-009 and MM-010, as well as a comprehensive analysis of the occurrence of SPMs in Celgene safety data and international patient databases.
According to the company, the CHMP opinion was based on extensive analysis of Celgene data in previously treated and newly diagnosed multiple myeloma patients.
The drug is approved in nearly 70 countries in combination with dexamethasone for the treatment of multiple myeloma patients who have received at least one prior therapy, while it is approved for treating patients whose disease has progressed after one therapy in Australia and New Zealand. It is also approved in many countries for treating transfusion-dependent anaemia.
CELG closed Thursday's regular trading session at $63.54, down $0.26 or 0.41 percent.
Link: http://www.rttnews.com/1720066/celgene-receives-positive-opinion-from-eu-for-revlimid-after-article-20-review.aspx
-
Safety Concerns Force Withdrawal Of Revlimid Application For Expanded Use In Europe
Jun 21, 2012 | The Myeloma Beacon
Celgene, the company that markets Revlimid in the United States and internationally, announced this morning that it has withdrawn its application in Europe to have the drug approved for use as initial therapy for newly diagnosed myeloma patients as well as for maintenance therapy.
The company also is postponing until next year a similar application it had intended to file in 2012 with the U.S. Food and Drug Administration (FDA).
The European application was withdrawn due to concerns raised by regulators about the link between Revlimid (lenalidomide) and second cancers (also known as second primary malignancies).
Celgene's announcement came as a surprise to many observers -- so much so that Celgene's stock declined more than 11 percent today.
The announcement means that near-term European use of Revlimid in newly diagnosed patients will be noticeably less than previously expected. It also indicates that concerns about risks associated with Revlimid maintenance therapy are continuing to persist.
In both Europe and the United States, Revlimid's only officially approved use as a myeloma treatment is for patients who have received at least one previous therapy.
In the United States, however, the drug can legally be used "off label" to treat newly diagnosed myeloma patients, and it very often is. A recent Beacon survey of its readers -- a majority of whom live in the U.S. -- found that 45 percent of them received Revlimid as one of their initial myeloma therapies.
Restrictions on the off-label use of drugs in Europe, however, mean that newly diagnosed European myeloma patients are treated much less frequently with Revlimid
Revlimid also is not specifically approved to be used as maintenance therapy. Nevertheless, its use as maintenance therapy has increased in the U.S. since initial results from three clinical trials showed that such treatment nearly doubles time to relapse. One of the three trials also has shown an overall survival benefit to Revlimid maintenance therapy (see related Beacon news).
It is data from these three trials -- known as the MM-015, IFM, and CALGB studies -- upon which the European application for Revlimid's expanded use was based.
It is also these three studies that have shown that Revlimid maintenance therapy -- either after stem cell transplantation, or after melphalan (Alkeran)-prednisone-Revlimid initial therapy -- increases the risk of a myeloma patient developing second cancers.
Both U.S. and European regulators have carried out reviews of Revlimid's safety during the past year, focusing on the drug's link to second cancers. Neither review led to any restrictions being placed on Revlimid's use. Both reviews, though, led to additional warnings being added to Revlimid's official U.S. and European prescribing information (see related Beacon news about the U.S. and European investigations).
When it announced the end of its review of Revlimid's safety, the European Medicines Agency (EMA) said that it "has confirmed that the benefit-risk balance for Revlimid (lenalidomide) remains positive within its approved patient population," and it noted that "the benefits of Revlimid, particularly improved survival, continue to outweigh the risks."
Today's announcement by Celgene, however, makes clear that a key part of the above statement from the EMA is the text that reads ""within its approved patient population."
Although the EMA appears comfortable with Revlimid's benefit-risk profile when the drug is used to treat myeloma patients who have had one previous therapy, the agency apparently is less convinced of Revlimid's benefit-risk profile when the drug is used as maintenance therapy or to treat newly diagnosed patients.
Celgene issued a brief press release early this morning announcing its decision to withdraw Revlimid's European application and providing an update about pomalidomide's regulatory status in the United States and Europe (see related Beacon news).
Later in the morning, Celgene executives hosted a conference call to provide further information about the recent developments and answer questions about them.
In a prepared statement at the beginning of the call, Celgene Chief Executive Officer Robert Hugin said that “In response to the need for more follow-up and mature data from the MM-015, IFM, and CALGB studies to allow [European authorities] to reach a clear benefit-risk conclusion, we have withdrawn the Revlimid newly diagnosed multiple myeloma application."
Mr. Hugin added that, despite the withdrawal of the European application, Celgene is "proceeding with submissions for Revlimid in newly diagnosed multiple myeloma in Switzerland, Australia, and other core markets."
For more information, see the complete compilation of Beacon articles with information about the Revlimid safety controversy as well as the complete text (below) of Mr. Hugin’s statement about the withdrawal of Revlimid's European application.
Partial Text of Statement By Robert Hugin, Chief Executive Officer, Celgene Corporation
(made during publicly broadcast conference call, June 21, 2012)In response to the need for more follow-up and mature data from the MM-015, IFM, and CALGB studies to allow the CHMP [Committee for Medicinal Products for Human Use] to reach a clear benefit-risk conclusion, we have withdrawn the Revlimid newly diagnosed multiple myeloma application. Our intention is to resubmit the application at the earliest possible time.
As we responded to each specific set of questions and discussed the progress of the application with our CHMP assessors, the 180-day questions made it clear that the follow-up and maturity of the studies with respect to the potential impact of second primary malignancies [SPMs] on the current survival trends had become a principle concern.
Based on these questions, we explored multiple approaches to more precisely define the positive benefit-risk ratio for Revlimid across the patient populations presented in our application.
Included in our responses were analyses that separated induction from maintenance indications and limited the potential approval to a subset of patients not eligible for stem cell transplant.
While there is strong consensus regarding the clinical benefits demonstrated by the studies in our application, discussions during and after our oral explanation further defined the need for additional follow-up to ensure that the current benefit-risk profile is not negatively impacted by SPMs.
We are proceeding with submissions for Revlimid in newly diagnosed multiple myeloma in Switzerland, Australia, and other core markets.
In the United States, we are currently reevaluating the timing and scope of our Revlimid newly diagnosed submission to the FDA and now anticipate submitting an application in 2013.
We are disappointed with this delay, but are very confident in the strength and importance of the data from these three trials, as evidenced by their recent publication in the New England Journal of Medicine.
These studies join the growing body of clinical evidence from a current total of seven completed Revlimid-based Phase 3 studies in multiple myeloma demonstrating positive patient benefits. In addition, there are approximately 15 ongoing Phase 3 trials evaluating Revlimid in combination with virtually every investigational drug in development for myeloma.
We are committed to ensuring the broadest access possible to Revlimid for myeloma patients around the world.
Link: http://www.myelomabeacon.com/news/2012/06/21/safety-concerns-force-withdrawal-of-revlimid-lenalidomide-application-for-expanded-use-in-europe/
-
Aug 4, 2011 | FDA
The U.S. Food and Drug Administration (FDA) is informing the public that we are aware of results from clinical trials conducted inside and outside the United States that found that patients treated with Revlimid (lenalidomide) may be at an increased risk of developing new types of cancer compared to patients who did not take the drug. FDA is currently reviewing all available information on this potential risk and will communicate any new recommendations once it has completed its review. At this time, FDA recommends that patients continue their Revlimid treatment as prescribed by their healthcare provider. The benefits and the risks of Revlimid should be carefully weighed when prescribing this drug. Healthcare professionals should be aware that Revlimid may increase the risk of developing another type of cancer. Revlimid is used to treat a type of blood disorder known as myelodysplastic syndrome. Revlimid is also used along with other drugs to treat people with the cancer known as multiple myeloma. Additional Information for Patients and CaregiversDo not stop taking Revlimid without talking to your healthcare professional.Discuss any questions or concerns about Revlimid with your healthcare professional.Continue to report any side effects you experience to the FDA MedWatch program using the information in the “Contact Us” box at the bottom of the page.Additional Information for Healthcare ProfessionalsPreliminary data derived from evaluation of outcomes after longer-term exposure to Revlimid and from controlled clinical trials conducted inside and outside the Unites States shows an increased incidence of some second primary malignancies, particularly acute myelogenous leukemia (AML) and B-cell lymphoma malignancies, when compared to controls.Since lenalidomide is an analogue of thalidomide, FDA is also currently reviewing all available information on this potential risk for thalidomide.At this time, there is no recommendation to delay, modify or restrict the use of Revlimid for patients being treated according to the FDA-approved indications. FDA is currently reviewing all available information on this potential risks and will communicate any new recommendations once it has completed its review.Continue to report adverse events involving Revlimid to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of the page.
Data Summary:
In summary, FDA is aware of the results of controlled clinical trials that showed a higher rate of second primary (new) malignancies among patients who were treated with Revlimid compared with those who were not. Data from evaluation of outcomes after long-term treatment also showed numerous second primary malignancies. Revlimid (lenalidomide) is approved for use, in combination with dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Revlimid is also approved for treatment of 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.
FDA is currently reviewing all available new information on this potential risk and at this time, recommends caution when interpreting these results. Currently, FDA believes the benefits of Revlimid continue to outweigh the potential risks. Patients should continue to follow the advice of their healthcare provider. FDA will communicate with the public as soon as we have more information.
Link: http://www.fda.gov/Drugs/DrugSafety/ucm250575.htm
-
May 7, 2012 | FDA
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.
In April 2011, FDA announced an ongoing safety review to evaluate the possible increased risk of second primary malignancies with Revlimid. FDA performed a comprehensive review of this safety issue (see Data Summary below).Additional Information for PatientsKnow that, in clinical trials of patients newly diagnosed with multiple myeloma, those patients treated with Revlimid had an increased risk of developing new cancers, particularly, acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma, compared to patients receiving a placebo.Contact your healthcare professional if you have any questions or concerns about Revlimid.Read the Medication Guide that comes along with your Revlimid prescription.Report side effects from Revlimid to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of this page.
Additional Information for Healthcare Professionals Know that, in clinical trials of patients newly diagnosed with multiple myeloma, those patients treated with Revlimid had an increased risk of developing second primary malignancies, particularly, acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma, compared to patients receiving a placebo.Monitor patients taking Revlimid for the development of second primary malignancies.Take into account both the potential benefit of Revlimid and the risk of second primary malignancies when considering treatment with Revlimid.Encourage patients to read the Medication Guide when they receive their Revlimid prescription.Please continue to report adverse events involving Revlimid to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of this page.
Data SummaryFDA 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).
Link: http://www.fda.gov/Drugs/DrugSafety/ucm302939.htm
-
FDA: Revlimid Linked to Second Cancers
May 8, 2012 | MedPage Today
By Michael Smith
Treatment of multiple myeloma with lenalidomide (Revlimid) as maintenance therapy is associated with an increased risk of second primary cancers, the FDA warned.
In three trials involving newly diagnosed patients initially treated with chemotherapy and stem cell transplantation, followed by maintenance lenalidomide or a placebo, the risk of a second primary cancer was increased about threefold, the agency said.ADVERTISEMENT
Trials involving relapsed/refractory patients – on which the drug's initial approval was based – did not show a significant increase in risk after adjustment for the length of time patients took the drug, the agency said.
A pooled analysis of the three maintenance trials showed that, as of Feb. 28, 2011, there had been 65 second primary malignancies among 824 lenalidomide patients and 19 among 665 patients in the treatment arms that did not include the drug.
The difference in incidence -- 7.9% versus 2.8% -- was significant at P<0.001.
The second primary cancers included acute myelogenous leukemia, myelodysplastic syndromes, and B-cell malignancies, the FDA reported, and, overall, 30 second primary hematologic malignancies were associated with lenalidomide, compared with two among patients not getting the drug.
There appears to be no difference in the incidence of nonmelanoma skin cancers or of solid tumors, the agency said.
The agency said the drug's label and patient medication guide will be amended to reflect the increased risk.
Patients and physicians should balance the benefit of the drug with the increased risk of second primary cancers, the agency suggested, and doctors should monitor patients on lenalidomide closely.
Link: http://www.medpagetoday.com/HematologyOncology/Myeloma/32576
-
FDA Issues Extensive Update About Revlimid And Second Cancers
May 7, 2012 | The Myeloma Beacon
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.
MORE INFORMATION
News articles about:
- second cancers
- RevlimidForum discussions about:
- Revlimid
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 relatedHealth 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 ofBeacon 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 malignanciesSafety Announcement
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 …
Data Summary
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).
Link: http://www.myelomabeacon.com/news/2012/05/07/fda-issues-extensive-update-about-revlimid-lenalidomide-and-second-cancers/
Article 20 Review
Second Primary Malignancies
Add recipients
Suggested