The European Commission (EC) has approved isatuximab (Sarclisa) 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.

Isatuximab is a monoclonal antibody (mAb) that binds to a specific epitope on the CD38 receptor of MM cells. 

In the Phase 3 ICARIA-MM study, isatuximab added to pom-dex (isatuximab combination therapy, n=154) 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) (HR 0.596, 95% CI: 0.44-0.81, p=0.001).

Isatuximab combination therapy also demonstrated a significantly greater overall response rate compared to pom-dex alone (60.4% vs. 35.3%, p<0.0001). In additional analyses,

Isatuximab combination therapy compared to pom-dex alone showed 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.

“As patients experience relapse of their multiple myeloma or become refractory to their current therapy, they become more difficult to treat with increasingly poor prognoses. In the ICARIA-MM trial, [isatuximab] combination therapy showed a treatment benefit consistent across relapsed and refractory multiple myeloma subgroups,” said Philippe Moreau, M.D., Department of Hematology, University Hospital of Nantes, France. “[Isatuximab] offers an important new treatment option and a potentially new standard of care for these patients with relapsed, refractory disease.”

As outlined in the Summary of Product Characteristics (SmPC), the most frequent adverse reactions observed with isatuximab (occurring in 20% or more of patients) are neutropenia (46.7%), infusion reactions (38.2%), pneumonia (30.9%), upper respiratory tract infection (28.3%), diarrhoea (25.7%) and bronchitis (23.7%).

The most frequent serious adverse reactions are pneumonia (9.9%) and febrile neutropenia (6.6%).

Isatuximab 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.

The EC marketing authorisation for isatuximab is applicable to the 27 member states of the European Union (EU), plus the UK, Iceland, Liechtenstein and Norway.

MM is the second most common haematologic malignancy, with more than 138,000 new cases worldwide each year.

In Europe, approximately 40,000 patients are diagnosed with MM yearly.

MM remains incurable in the vast majority of patients, resulting in significant disease burden.

Isatuximab is a mAb that binds to a specific epitope on the CD38 receptor.

CD38 is highly and uniformly expressed on MM cells, making it a potential target for antibody-based therapeutics such as isatuximab.

It is designed to induce programmed tumour cell death (apoptosis) and immunomodulatory activity.

In addition to the EU, isatuximab has also been approved in the U.S., Switzerland, Canada and Australia in combination with pom-dex for the treatment of certain adults with relapsed refractory MM.

Isatuximab continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.

It is also under investigation for the treatment of other haematologic malignancies and solid tumours.

The safety and efficacy of these additional uses have not been reviewed by any regulatory authority worldwide.

Source: Sanofi