What is isatuximab (Sarclisa®)?
Isatuximab is a monoclonal antibody (mAb, a laboratory manufactured antibody) drug indicated together with pomalidomide and dexamethasone for the treatment of multiple myeloma. It is administered to adults who have received at least two previous lines of therapy, including lenalidomide and a proteasome inhibitor, and whose myeloma has progressed since receiving the last treatment 1,4. Isatuximab is also recommended in combination with carfilzomib and dexamethasone, for the treatment of adult multiple myeloma patients who have received at least one prior line of therapy 2,4.
As multiple myeloma is considered a ‘rare disease’ because it affects such a small number of people, isatuximab was granted ‘orphan drug designation’ by the European Commission in 2014. An orphan drug designation is a status assigned to medicines developed for rare disease conditions that affect fewer than 5 patients per 10,000 inhabitants in the EU1. It received a marketing authorisation valid throughout the EU on 30 May 20203.
How does isatuximab work?
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 destruction2.
What are the benefits of isatuximab?
The safety and efficacy of isatuximab has been evaluated in several studies. In the ICARIA-MM study4 that included 307 participants, isatuximab was administered in combination with pomalidomide and dexamethasone. Patients who received isatuximab lived about 12 months without worsening of their myeloma, while for patients who did not receive isatuximab this lasted about 6 months.
What are the side-effects of isatuximab?
The most common side effects of isatuximab are1,2,3,4:
- neutropenia (low levels of neutrophils, a type of white blood cell also known as an immune 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 and febrile neutropenia (low white blood cell counts with fever).
How and when is isatuximab given?
Isatuximab is given by infusion (drip) at a dose of 10 mg/kg of body weight once per week for the first cycle of treatment. Cycles are defined as periods of treatment (usually 28 days). After the initial cycle, one dose of isatuximab is given every two weeks. Before infusion, patients may be given medicines to reduce the risk of infusion-related reactions. The doctor may slow down the infusion or stop treatment in case of infusion-related reactions2.
References
Attal, M. et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. The Lancet 394, 2096–2107 (2019)
“Dailymed – SARCLISA- Isatuximab Injection, Solution, Concentrate”. Dailymed.Nlm.Nih.Gov, 2022: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0473462-6f9d-4eca-a5bf-8620aea68e8a.
“Sarclisa – European Medicines Agency”. European Medicines Agency, 2022: https://www.ema.europa.eu/en/medicines/human/EPAR/sarclisa.
Moreau P, et al. “Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.” Lancet. 2021;397(10292):2361-2371.
