Isatuximab, sold under the brand name Sarclisa among others, is a monoclonal antibody medication used for the treatment of multiple myeloma. It is administered by either intravenous injection or subcutaneous injection. It is a CD38-directed cytolytic antibody. The most common side effects include neutropenia (low levels of neutrophils, a type of white blood cell), infusion reactions, pneumonia (infection of the lungs), upper respiratory tract infection (such as nose and throat infections), diarrhea and bronchitis (inflammation of the airways in the lungs). Isatuximab was approved for medical use in the United States and the European Union in 2020. The subcutaneous form was approved for medical use in the United States in June 2026.
Medical uses In the United States, isatuximab (intravenous) is indicated, in combination with pomalidomide and dexamethasone for the treatment of adults with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor; 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; or in combination with bortezomib, lenalidomide, and dexamethasone for the treatment of adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant. In the United States, isatuximab (subcutaneous) is indicated, in combination with pomalidomide and dexamethasone, for the treatment of adults with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor; 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; or in combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant. In the European Union it is indicated, in combination with pomalidomide and dexamethasone, for the treatment of adults with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy; in combination with carfilzomib and dexamethasone, for the treatment of adults with multiple myeloma who have received at least one prior therapy; in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; or in combination with bortezomib, lenalidomide, and dexamethasone, for the induction treatment of adults with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.
Side effects Adverse reactions to isatuximab may include neutropenia, infusion-related reactions and/or secondary primary malignancies. Of these three the most commonly occurring ones are the infusion-related reactions. Examples of the most frequent symptoms of infusion-related reactions are dyspnea, cough, chills, and nausea, while the severest signs and symptoms included hypertension and dyspnea.
History It was granted orphan drug designation for multiple myeloma by the European Medicines Agency in April 2014, and by the US Food and Drug Administration (FDA) in December 2016. In March 2020, it was approved for medical use in the United States. The U.S. Food and Drug Administration (FDA) approved isatuximab in March 2020, based on evidence from a clinical trial (NCT02990338) of 307 subjects with previously treated multiple myeloma. The trial was conducted at 102 sites in Europe, North America, Asia, Australia and New Zealand. The trial evaluated the efficacy and side effects of isatuximab in subjects with previously treated multiple myeloma. Subjects were randomly assigned to receive either isatuximab (in combination with pomalidomide and low-dose dexamethasone) or active comparator (pomalidomide and low-dose dexamethasone). Treatment was administered in both groups in 28-day cycles until disease progression or unacceptable toxicity. Both subjects and health care providers knew which treatment was given. The trial measured the time patients lived without the cancer growing (progression-free survival or PFS). It was approved for medical use in the European Union in May 2020.
Structure and reactivity The structure of isatuximab consists of two identical immunoglobulin kappa light chains and also two equal immunoglobulin gamma heavy chains. Chemically, isatuximab is similar to the structure and reactivity of daratumumab, hence both drugs show the same CD38 targeting. However, isatuximab shows a more potent inhibition of its ectozyme function. The latter gives potential for some non-cross reactivity. Isatuximab shows action of an allosteric antagonist with the inhibition of the CD38 enzymatic activity. Additionally, isatuximab shows potential where it can induce apoptosis without cross linking. Lastly, Isatuximab reveals direct killing activity when a larger increase in apoptosis is detected in CD38 expressing cancer cells. Furthermore, isatuximab demonstrated a dose dependent inhibition of CD38 enzymatic activity. However, daratumumab with the same experimental conditions shows a more limited inhibition without a dose response.
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