On 14 November 2024, the Committee for Medicinal Products for Human Use (CHMP) recommended adding a new indication for isatuximab, a monoclonal antibody treatment marketed by Sanofi as Sarclisa ®. The CHMP is the European Medicines Agency’s committee playing a significant role in the assessment and authorisation of human medicines. The new indication for isatuximab is for first-line treatment of newly diagnosed myeloma patients who are ineligible for stem cell transplant, in combination with bortezomib, lenalidomide and dexamethasone.

Isatuximab binds to the CD38 protein, which is present on the surface of myeloma cells. By binding to this protein, isatuximab induces the death of myeloma cancer cells (also called apoptosis). Also, by binding to the CD38 protein on the surface of the myeloma cell, isatuximab activates the immune system by marking the myeloma cells for destruction.

Isatuximab is already approved in Europe for use:

• Together with pomalidomide and dexamethasone for the treatment of relapsed/refractory myeloma. It is administered to patients who have received at least two previous lines of therapy, including lenalidomide and a proteasome inhibitor, e.g. bortezomib, and whose myeloma has progressed since receiving the last treatment.
• In combination with carfilzomib and dexamethasone, for the treatment of myeloma patients who have received at least one prior line of therapy.

In September 2024, the US Food and Drug Administration (FDA) approved isatuximab in combination with bortezomib, lenalidomide and dexamethasone for the treatment of patients with new myeloma who are ineligible for stem cell transplant, which was the first approval for isatuximab as first-line treatment in this setting. If the European Commission approve the new indication in Europe, this could mean another treatment option for newly diagnosed myeloma patients who are transplant-ineligible with potential for increased survival rates and better treatment responses.

The CHMP recommendation is based on the results of the IMROZ trial, which is a phase III clinical trial across 93 sites in 21 countries, including 13 European countries. The trial was comparing a combination of bortezomib, lenalidomide, and dexamethasone with and without isatuximab for transplant ineligible newly diagnosed myeloma patients.

The main trial results currently available show that 63.2% of patients receiving isatuximab were alive after five years, compared to 45.2% of patients not receiving isatuximab. However, in patients who have high-risk cytogenetics, there was no survival benefit found, and further study was recommended. In all patient groups, overall response rates were similar, however the isatuximab treatment led to higher rates of complete or better responses, and higher rates of minimal residual disease negative responses, which is where there is almost undetectable myeloma.

There were higher rates of serious adverse events in patients receiving isatuximab, (70.7% compared with 67.4% in patients not receiving isatuximab). Side effects of isatuximab include neutropenia (low levels of neutrophils, a type of white blood cell), infusion reactions (occur during or shortly after infusion), pneumonia (infection of the lungs), upper respiratory tract infection (such as nose and throat infections), diarrhoea, bronchitis (inflammation of the airways in the lungs). The most common serious side effects are pneumonia (20% of patients) and febrile neutropenia (4%) (low white blood cell counts with fever).

The European Commission now has approximately 60 days in which to consider and adopt the CHMP Commission recommendation. If adopted by the Commission, pricing and reimbursement decisions will then be taken at country level.