The REVLIMID® Marketing Authorisation has been updated to include this new indication, which expands on the existing multiple myeloma indications as combination therapy for the treatment of those not eligible for transplant who are newly diagnosed, or have received at least one prior therapy.
Multiple myeloma is an incurable and life-threatening blood cancer that
is characterised by tumour proliferation and suppression of the immune
system.1 It is a rare but deadly disease: around 39,000
people are diagnosed with multiple myeloma in
For patients who are newly diagnosed with multiple myeloma and eligible for ASCT, key treatment goals are to delay disease progression and ultimately achieve long-term control over multiple myeloma.5 These patients typically receive induction therapy and high-dose chemotherapy with melphalan followed by ASCT. This treatment approach has been an established standard of care for over 20 years.6 Considering that over half of those patients who relapse do so within 2 to 3 years of ASCT,7,8 the approval of a maintenance therapy for use after ASCT that may delay disease progression represents a major advance for these patients.
"After ASCT, most patients will still see their disease recur or
progress. We now have an opportunity to enhance immune function and
delay disease progression by controlling residual malignant cells and
slowing tumour growth. REVLIMID® has been shown
to increase progression-free survival after ASCT in clinical trials.
Having a licensed therapy for use in this very important setting means
we now have the opportunity to delay disease progression by sustaining
the response," says Professor
In both studies, the primary efficacy endpoint in the study was
progression-free survival (PFS) from transplant to the date of disease
progression or death, whichever occurred first. REVLIMID®
monotherapy as maintenance treatment post-ASCT significantly reduced the
risk of disease progression or death in patients with multiple myeloma,
leading to the studies being unblinded based on passing their
pre-specified boundary for superiority at interim analysis. The updated
PFS, using a cut-off of
Individual studies were not powered for an overall survival (OS)
endpoint. Using a cut-off of
In both of these phase III studies, the safety profile was in line with other clinical data in newly diagnosed non-stem cell transplant and a post-approval safety study in relapsed/refractory multiple myeloma. The most commonly reported adverse events in these two studies were haematological, and included neutropenia and thrombocytopenia. The most commonly reported non-haematological adverse events were infections. An increased incidence rate of haematological second primary malignancies (SPMs) was also observed in the REVLIMID® group compared with the placebo group in both studies. However, the EC decision confirms that the benefit-risk ratio for REVLIMID® is positive in this expanded indication.
About CALGB 100104
CALGB 100104 was a phase III, randomised, controlled, double-blind,
multi-centre study conducted in 47 centres in
About IFM 2005-02
IFM 2005-02 was a phase III, controlled, double-blind, multi-centre
study conducted in 77 centres across 3 countries in
REVLIMID® as combination therapy is approved in
REVLIMID® is also approved in
In addition, REVLIMID® is approved in
REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.
ADDITIONAL IMPORTANT SAFETY INFORMATION based on EU SmPC
REVLIMID® (lenalidomide) is contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients in the formulation.
REVLIMID® (lenalidomide) is contraindicated during pregnancy, and also in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met.
Warnings and precautions
Pregnancy: the conditions of the Pregnancy Prevention Programme must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential.
Cardiovascular disorders: patients with known risk factors for myocardial infarction or thromboembolism should be closely monitored.
Neutropenia and thrombocytopenia: complete blood cell counts should be performed every week for the first 8 weeks of treatment and monthly thereafter to monitor for cytopenias. A dose reduction may be required.
Infection with or without neutropenia: all patients should be advised to seek medical attention promptly at the first sign of infection.
Renal impairment: monitoring of renal function is advised in patients with renal impairment.
Thyroid disorders: optimal control of co-morbid conditions influencing thyroid function is recommended before start of treatment. Baseline and ongoing monitoring of thyroid function is recommended.
Tumour lysis syndrome: patients with high tumour burden prior to treatment should be monitored closely and appropriate precautions taken.
Allergic reactions: patients who had previous allergic reactions while treated with thalidomide should be monitored closely.
Severe skin reactions: REVLIMID® (lenalidomide) must be discontinued for exfoliative or bullous rash, or if SJS or TEN is suspected, and should not be resumed following discontinuation for these reactions. Interruption or discontinuation of lenalidomide should be considered for other forms of skin reaction depending on severity. Patients with a history of severe rash associated with thalidomide treatment should not receive lenalidomide.
Lactose intolerance: patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Second primary malignancies (SPM): the risk of occurrence of hematologic SPM must be taken into account before initiating treatment with REVLIMID® (lenalidomide) either in combination with melphalan or immediately following high-dose melphalan and autologous stem cell transplant (ASCT). Physicians should carefully evaluate patients before and during treatment using standard cancer screening for occurrence of SPM and institute treatment as indicated.
Hepatic disorders: dose adjustments should be made in patients with renal impairment. Monitoring of liver function is recommended, particularly when there is a history of or concurrent viral liver infection or when REVLIMID® (lenalidomide) is combined with medicinal products known to be associated with liver dysfunction.
Newly diagnosed multiple myeloma patients: patients should be carefully assessed for their ability to tolerate REVLIMID® (lenalidomide) in combination, with consideration to age, ISS stage III, ECOG PS≤2 or CLcr < 60 mL/min.
Cataract: regular monitoring of visual ability is recommended.
Summary of the safety profile in multiple myeloma
Newly diagnosed multiple myeloma: patients who have undergone ASCT treated with REVLIMID® (lenalidomide) maintenance:
Newly diagnosed multiple myeloma: patients who are not eligible for transplant treated with REVLIMID® (lenalidomide) in combination with low dose dexamethasone:
Newly diagnosed multiple myeloma: patients who are not eligible for ASCT treated with REVLIMID® (lenalidomide) in combination with melphalan and prednisone:
Patients with multiple myeloma who have received at least one prior therapy:
Paediatric population: REVLIMID® (lenalidomide) should not be used in children and adolescents from birth to less than 18 years.
Older people with newly diagnosed multiple myeloma: for patients older than 75 years of age treated with REVLIMID® (lenalidomide) in combination with dexamethasone, the starting dose of dexamethasone is 20 mg/day on Days 1, 8, 15 and 22 of each 28-day treatment cycle. No dose adjustment is proposed for patients older than 75 years who are treated with REVLIMID® (lenalidomide) in combination with melphalan and prednisone.
Older people with multiple myeloma who have received at least one prior therapy: care should be taken in dose selection and it would be prudent to monitor renal function.
Patients with renal impairment: care should be taken in dose selection and monitoring of renal function is advised. No dose adjustments are required for patients with mild renal impairment and multiple myeloma. Dose adjustments are recommended at the start of therapy and throughout treatment for patients with moderate or severe impaired renal function or end stage renal disease.
Patients with hepatic impairment: REVLIMID® (lenalidomide) has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations.
Please refer to the Summary of Product Characteristics for full European prescribing information.
Celgene International Sàrl, located in Boudry,
This press release contains forward-looking statements, which are
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1 Palumbo A, et al. N Engl J Med. 2011;364:1046-1060.
2 Ferlay J, et al. Eur J Cancer. 2013;49:1374-1403
3 Moreau P, et al. Ann Oncol. 2013; 24 (Suppl 6): vi133-vi137
4 Moreau P, et al. Ann Oncol. 2013; 24 (Suppl 6): vi133-vi137
5 Stewart AK, et al. Blood. 2009;114:5436-5443.
6 Bird JM, et al. Br
7 Attal M, et al. Blood. 2006 Nov 15;108(10):3289-94
8 Child JA, et al. N Engl J Med. 2003; 348:1875-1883
9 McCarthy PL, et al. N Engl J Med. 2012;366(19):1770-1781. CALGB is the cooperative group Cancer and Leukemia Group B (now known as Alliance).
10 Attal M, et al. N Engl J Med. 2012;366(19):1782-1791. IFM is the cooperative group Intergroupe Francophone du Myélome.
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