Subcutaneous Isatuximab Approved for Several Multiple Myeloma Indications

The FDA approved isatuximab-irfc as part of three different combination regimens for multiple myeloma.

The U.S. Food and Drug Administration (FDA) has approved isatuximab-irfc (Sarclisa Escena) for subcutaneous injection for three multiple myeloma indications:

  • in combination with pomalidomide (Pomalyst) and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy that included lenalidomide (Revlimid) and a proteasome inhibitor;
  • in combination with carfilzomib (Kyprolis) and dexamethasone for adults with relapsed or refractory multiple myeloma that has been previously treated with one to three prior lines of therapy; and
  • in combination with bortezomib (Velcade), lenalidomide, and dexamethasone for adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
A photomicrograph of multiple myeloma cells on a histopathology slide.

Isatuximab-irfc is a monoclonal antibody that targets the protein CD38, which is expressed on the surfaces of hematopoietic and multiple myeloma cells. Isatuximab-irfc can induce cell death though a variety of immune mechanisms, including antibody-dependent cell-mediated cytotoxicity (ADCC). An intravenously administered formulation of isatuximab-irfc, first described in the American Association for Cancer Research (AACR) journal Clinical Cancer Research, was previously approved for several multiple myeloma indications. The approval of the subcutaneous formulation gives eligible patients the option to receive therapy in less time than is required for intravenous infusion.

Dexamethasone is a corticosteroid often used in the treatment of hematological malignancies. Lenalidomide and pomalidomide are immune-modulating drugs that can kill and slow the growth of multiple myeloma cells. Both carfilzomib and bortezomib are proteasome inhibitors that disrupt the cell’s ability to break down proteins, leading to the buildup of cellular waste and subsequent cell death.

The approval of isatuximab-irfc was based on results from three clinical trials.

IRAKLIA—a randomized, open-label, noninferiority, phase III clinical trial—evaluated either intravenous or subcutaneous administration of isatuximab-irfc with pomalidomide and dexamethasone in 531 patients with relapsed and/or refractory multiple myeloma who had received at least one prior line of therapy that included lenalidomide and a proteasome inhibitor. The patients were randomly assigned 1:1 to receive isatuximab-irfc in either an intravenous or subcutaneous form with pomalidomide and dexamethasone.

After a median follow-up of 12 months, the overall response rate (ORR) was similar between the subcutaneous arm (71.1%) and the intravenous arm (70.5%). The subcutaneous form of isatuximab-irfc maintained a minimum plasma concentration that was, on average, 53% higher than that of the intravenous isatuximab-irfc.

IZALCO—a randomized, open-label, phase II clinical trial—evaluated the efficacy of subcutaneous isatuximab-irfc with carfilzomib and dexamethasone in 74 patients who had relapsed and/or refractory multiple myeloma. All patients received subcutaneous isatuximab-irfc, and 79.7% had experienced a treatment response during the median 10 months of follow-up.

ISASOCUT—a single-arm, investigator-sponsored, phase II clinical trial—evaluated isatuximab-irfc in 74 adult patients with newly diagnosed multiple myeloma who were ineligible for stem cell transplantation. After a median follow-up of 12 months, the ORR was 97.3%.

The subcutaneous formulation of isatuximab-irfc is approved for administration via either the CirCLIQ on-body delivery system, which injects the combination therapy automatically, or via a manual syringe and infusion set. The recommended dose of isatuximab-irfc is 1,400 mg across indications, in combination with other regimens as described by the label’s prescribing information.

  • When combined with pomalidomide and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy that included lenalidomide and a proteasome inhibitor, 1,400 mg of subcutaneous isatuximab-irfc should be given weekly for the first month, followed by once every two weeks thereafter.
  • When combined with carfilzomib and dexamethasone for adults with relapsed or refractory multiple myeloma that has been previously treated with one to three prior lines of therapy, 1,400 mg of subcutaneous isatuximab-irfc should be given weekly for the first month, followed by once every two weeks thereafter.
  • When combined with bortezomib, lenalidomide, and dexamethasone for adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, 1,400 mg of subcutaneous isatuximab-irfc should be given weekly for the first month; once every two weeks for the next 11 months; and once a month thereafter.

All treatment regimens should continue until disease progression or unacceptable toxicity.

The prescribing information for pomalidomide and lenalidomide each carries a boxed warning for embryo-fetal toxicity, as well as venous and arterial thromboembolism. Lenalidomide carries an additional boxed warning for hematologic toxicity.

Multiple myeloma is a cancer that develops within the bone marrow when excessive abnormal B cells accumulate, which then form tumors throughout multiple bones. While stem cell transplants (also called bone marrow transplants) can be effective against multiple myeloma, many patients are not eligible for this intensive procedure due to their age or physical fitness. According to federal statistics, it was estimated that 36,000 individuals would be diagnosed with myeloma and 10,850 patients would die of the disease in the United States in 2026.

The FDA rendered its decision on July 9, 2026. Check this resource for updated information on all therapeutics regulated by the FDA.