Isatuximab, sold under the brand name Sarclisa, is a monoclonal antibody (mAb) medication for the treatment of multiple myeloma.
[9] [needs update] In the United States it is indicated, in combination with pomalidomide and dexamethasone (video about this from ASH 2022), for the treatment of adults with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
[10][11][12] It is also indicated in combination with carfilzomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
[13] As of September 2024, it is also approved in combination with lenalidomide, bortezomib and dexamethasone for newly diagnosed patients inelibible for a hematopoietic stem cell transplantation.
[14] In the European Union it is indicated, in combination with pomalidomide and dexamethasone, for the treatment of adults with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI) and have demonstrated disease progression on the last therapy.
[4][15] Researchers started a Phase I study with isatuximab in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma (MM).
The results during the Phase I trial showed that 26 out of the 45 patients discontinued the treatment due to progression of the disease.
[17] A Phase III combination trial for plasma cell myeloma is comparing pomalidomide and dexamethasone with and without isatuximab is in progress with a completion date of 2021.
[10][11][12][21] The U.S. Food and Drug Administration (FDA) approved isatuximab-irfc in March 2020, based on evidence from a clinical trial (NCT02990338) of 307 subjects with previously treated multiple myeloma.
[12] The trial evaluated the efficacy and side effects of isatuximab-irfc in subjects with previously treated multiple myeloma.
[22] Lastly, Isatuximab reveals direct killing activity when a larger increase in apoptosis is detected in CD38 expressing cancer cells.
[25] The binding with the CD38 receptor is mainly via the gamma heavy chains and are more potent than other CD38 antibodies such as daratumumab which can inhibit the enzymatic activity of CD38.
[6] Cancer of the blood that is distinguished by an overproduction of malignant plasma cells in the bone marrow is called multiple myeloma.
[27] CD38 was first described as an activation marker, but later the molecule displayed functions in adhesion to endothelial CD31 proteins, e.g. as an aiding component of the synapse complex, as well as an ectoenzyme implicated in the metabolism of extracellular NAD+ and cytoplasmic NADP.
The tumour cells can evade the immune system, possibly due to adenosine, an immunosuppressive molecule that arises as a product of the ectoenzymatic activity of CD38.
[29] According to the FDA, isatuximab-irfc alone has reduced ADCC and direct tumor cell killing activity in vitro in comparison to when it is combined with pomalidomide.
As well as increased anti-tumor activity as opposed to isatuximab-irfc or pomalidomide only in a human multiple myeloma xenograft model.
When isatuximab is at a constant state it is expected that the ≥99% elimination will occur approximately two months after the last dose was administered.
It is necessary to carefully monitor the patient in case of an overdose and to employ clinically indicated symptomatic and supportive procedures.
Restrictions for the use of isatuximab is that the patients have to be adults who have at least received two previous treatments with lenalidomide and a proteasome inhibitor.
[30] A Phase III study of patients with refractory and relapsed MM, who were resistant to lenalidomide and a proteasome inhibitor, and could not have received daratumumab, another anti-CD38 monoclonal antibody was published in 2019 (ICARIA-MM).