Drugs Xagena
The European Commission ( EC ) has approved Revlimid ( Lenalidomide ) as monotherapy for the maintenance treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation ( ASCT ). Revlimid is the first and only licensed maintenance treatment available to these patients.
Multiple myeloma is an incurable and life-threatening blood cancer that is characterised by tumour proliferation and suppression of the immune system. It is a rare but deadly disease: around 39,000 people are diagnosed with multiple myeloma in Europe, and around 24,000 people die from the disease each year.
The median age at diagnosis in Europe is between 65 and 70 years.
In Europe, patients who are fit and in good clinical condition are typically considered eligible for ASCT.
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. 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.
Considering that over half of those patients who relapse do so within 2 to 3 years of ASCT, the approval of a maintenance therapy for use after ASCT that may delay disease progression represents a major advance for these patients.
The EC decision to approve Revlimid as monotherapy for multiple myeloma in the post-ASCT setting was based on the results of two cooperative group-led studies, CALGB 1001049 and IFM 2005-02.10
CALGB 100104 was a phase III, controlled, double-blind, multi-centre study of 460 patients with newly diagnosed multiple myeloma undergoing ASCT who were randomized to receive continuous daily treatment with Lenalidomide or placebo until relapse or intolerance.
IFM 2005-02 was an international, phase III, controlled, double-blind, multi-centre study of 614 patients newly diagnosed with multiple myeloma who were randomized to receive a 2-month consolidation regimen post-ASCT of Lenalidomide monotherapy, followed by continuous daily treatment with either Lenalidomide or placebo until relapse or intolerance.
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.
Lenalidomide 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 progression-free survival, using a cut-off of 1 February 2016 continues to show a PFS advantage:
CALGB 100104: after 81.6 months of follow up, median PFS was 56.9 months ( 95% CI 41.9, 71.7 ) in the Lenalidomide arm versus 29.4 months ( 95% CI 20.7, 35.5 ) in the placebo arm ( hazard ratio, HR=0.61; 95% CI 0.48, 0.76; p less than 0.001 ).
IFM 2005-02: after 96.7 months of follow up, median PFS was 44.4 months ( 95% CI 39.6, 52.0 ) in the Lenalidomide arm versus 23.8 months ( 95% CI 21.2, 27.3 ) in the placebo arm ( HR=0.57; 95% CI 0.47, 0.68; p less than 0.001 ).
Individual studies were not powered for an overall survival ( OS ) endpoint.
Using a cut-off of 1 February 2016, a descriptive analysis showed that the median overall survival in the CALGB 100104 was 111.0 months ( 95% CI, 101.8, not estimable ) for patients who received Lenalidomide versus 84.2 ( 95% CI 71.0, 102.7 ) in the placebo arm ( HR=0.61; 95% CI 0.46, 0.81; p less than 0.001).
In the IFM 2005-02 study, median overall survival was 105.9 months ( 95% CI, 88.8, not estimable ) for patients who received Lenalidomide versus 88.1 ( 95% CI 80.7, 108.4 ) in the placebo arm ( HR=0.90; 95% CI 0.72, 1.13; p=0.355, not significant ).
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 Lenalidomide group compared with the placebo group in both studies.
However, the European Commission decision has confirmed that the benefit-risk ratio for Revlimid is positive in this expanded indication. ( Xagena )
Source: Celgene, 2017
XagenaMedicine_2017
