The European Commission ( EC ) has approved Sarclisa ( Isatuximab ) in combination with Pomalidomide and Dexamethasone ( Pom-Dex ) for the treatment of adult patients with relapsed and refractory multiple myeloma ( MM ) who have received at least two prior therapies including Lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy.
Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor of myeloma cells. CD38 is highly and uniformly expressed on MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa. It is designed to induce programmed tumor cell death ( apoptosis ) and immunomodulatory activity.
In the phase 3 ICARIA-MM study, Sarclisa added to Pom-Dex ( Sarclisa combination therapy, n=154 ) has demonstrated a statistically significant improvement of progression-free survival ( PFS ), with a median PFS of 11.53 months compared to 6.47 months with Pom-Dex alone ( n=153 ) ( hazard ratio, HR 0.596, 95% CI: 0.44-0.81, p=0.001 ).
Sarclisa combination therapy has also demonstrated a significantly greater overall response rate compared to Pom-Dex alone ( 60.4% vs. 35.3%, p less than 0.0001 ).
In additional analyses, Sarclisa combination therapy compared to Pom-Dex alone has shown a treatment benefit consistent across select subgroups reflective of real-world practice, including patients with high risk cytogenetics, those aged 75 years and older, patients with renal insufficiency and patients who were refractory to Lenalidomide.
The most frequent adverse reactions observed with Sarclisa ( occurring in 20% or more of patients ) are neutropenia ( 46.7% ), infusion reactions ( 38.2% ), pneumonia ( 30.9% ), upper respiratory tract infection ( 28.3% ), diarrhea ( 25.7% ) and bronchitis ( 23.7% ).
The most frequent serious adverse reactions are pneumonia ( 9.9% ) and febrile neutropenia ( 6.6% ).
Sarclisa is administered by intravenous ( IV ) administration and is dosed at 10 mg/kg, in combination with Pom-Dex, every week for four weeks and then every two weeks, until disease progression or unacceptable toxicity.
Assuming no rate adjustments based on infusion-related reactions, the first infusion takes three to four hours, the second infusion takes less than two hours, and the remaining infusions can decrease to 75 minutes from the third infusion onwards.
A treatment cycle is 28 days.
Multiple myeloma is the second most common hematologic malignancy, with more than 138,000 new cases worldwide each year.
In Europe, approximately 40,000 patients are diagnosed with multiple myeloma yearly.
Multiple myeloma remains incurable in the vast majority of patients, resulting in significant disease burden. ( Xagena )
Source: Sanofi, 2020