Drugs Xagena
The European Commission has approved Empliciti ( Elotuzumab ) for the treatment of multiple myeloma as combination therapy with Revlimid ( Lenalidomide ) and Dexamethasone in patients who have received at least one prior therapy.
Empliciti is now the first and only immunostimulatory antibody approved for multiple myeloma in the European Union ( EU ).
The approval is based on data from the randomized, open-label, phase 3 ELOQUENT-2 study, which evaluated Elotuzumab in combination with Lenalidomide and Dexamethasone ( ERd ) versus Lenalidomide and Dexamethasone ( Rd ) alone.
The co-primary endpoints of this study, progression-free survival ( PFS ) as assessed by hazard ratio ( HR ) and overall response rate ( ORR ), were achieved, with extended follow-up data showing a 53% relative improvement in PFS rate at three years ( 23% versus 15% ).
Additionally, a pre-specified interim analysis for overall survival ( OS ) found a positive trend favoring the Elotuzumab combination versus Rd alone ( HR=0.77 [ 95% CI: 0.61, 0.97, p=0.0257 ] ), though at the time of the interim analysis, the overall survival endpoint had not reached the pre-determined threshold for statistical significance.
Patients will continue to be followed for survival, and the final analysis is pending.
Elotuzumab with Lenalidomide and Dexamethasone is associated with the following Warnings and Precautions: infusion reactions, infections, second primary malignancies, hepatotoxicity, interference with determination of complete response, pregnancy/females and males of reproductive potential, and adverse reactions.
In ELOQUENT-2, Elotuzumab was evaluated in patients who had received one to three prior therapies. The study demonstrated that the ERd regimen resulted in a 32% reduction in the risk of disease progression or death compared to Rd alone ( HR=0.68 [ 97.61% CI: 0.55, 0.85, p=0.0001 ] ).
The ERd regimen also showed a 21% relative improvement in PFS rate at one year ( 68% versus 56% ) and a 50% relative improvement in PFS rate at two years ( 39% versus 26% ) compared to Rd alone.
The ERd regimen demonstrated a significant improvement in ORR of 78.5% ( 95% CI: 73.6-82.9; p=0.0002 ) versus 65.5% in the Rd arm ( 95% CI: 60.1-70.7 ).
The extended follow-up analysis also showed ERd had a median delay of one year in the time to next treatment compared to Rd alone: 33.35 months ( 95% CI: 26.15, 40.21 ) versus 21.22 months ( 95% CI: 18.07, 23.20 ) ( HR=0.62 [ 95% CI: 0.50, 0.77 ] ).
Discontinuation rates due to adverse reactions were similar across the ERd and Rd arms ( 8.7%, 12.9% ). The most common adverse reactions ( all grades ) in ERd and Rd ( more than 10% ), respectively, were diarrhea ( 59.2%, 49.3% ), pyrexia ( 43.0%, 27.7% ), fatigue ( 40.0%, 34.7% ), cough ( 33.2%, 20.3% ), nasopharyngitis ( 29.5%, 27.7% ), upper respiratory tract infection ( 25.2%, 22.7% ), lymphopenia ( 17.6%, 13.6% ), headache ( 17.2%, 9.6% ), pneumonia ( 15.6%, 12.9% ) and herpes zoster ( 10.0%, 5.7% ).
Infusion reactions occurred in 10% of patients treated with ERd; these adverse reactions were grade 3 or lower ( grade 3, 1%; grade 4, 0% ).
In the trial, 1% of patients discontinued due to infusion reactions, and 5% of patients required interruption of the administration of Elotuzumab for a median of 25 minutes.
ELOQUENT-2 is a phase 3, open-label, randomized study evaluating Elotuzumab in combination with Rd versus Rd alone in patients with relapsed or refractory multiple myeloma.
The trial randomized 646 patients who had received one to three prior therapies. Patients were randomized 1:1 to receive either Elotuzumab 10 mg/kg in combination with Rd or Rd alone in 4-week cycles until disease progression or unacceptable toxicity. Baseline patient demographics and disease characteristics were well balanced between treatment arms and included a meaningful portion of patients who were greater than or equal to 65 years old, had high-risk cytogenetics and/or were refractory to the most recent line of therapy.
The minimum follow-up for all study subjects was 24 months.
The co-primary endpoints were progression-free survival, as assessed by hazard ratio, and ORR, as determined by a blinded Independent Review Committee using the European Group for Blood and Marrow Transplantation response criteria.
Elotuzumab is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 ( SLAMF7 ), a cell-surface glycoprotein.
SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.
Elotuzumab has a dual mechanism-of-action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Elotuzumab also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.
Multiple myeloma is a hematologic cancer that develops in the bone marrow. Common symptoms of multiple myeloma include bone pain, fatigue, kidney impairment and infections.
Despite advances in multiple myeloma treatment over the last decade, less than half of patients survive for five or more years after diagnosis.
Patients often experience a cycle of remission and relapse, and once a patient first relapses, their prognosis worsens with progressively faster relapses through each subsequent line of therapy.
It is estimated that annually, more than 114,200 new cases of multiple myeloma are diagnosed, and more than 80,000 people die from the disease globally. ( Xagena )
Source: BMS, 2016
XagenaMedicine_2016
