FDA Accepts Isatuximab for Priority Review for Treatment of Transplant-Ineligible Multiple Myeloma


Isatuximab is used in combination with bortezomib, lenalidomide, and dexamethanose.

The FDA has accepted for priority review the supplemental biologics license application for isatuximab (Sarclisa; Sanofi-aventis), in combination with bortezomib (Velcade; Millennium/Takeda and Janssen Pharmaceutical Companies), lenalidomide (Revlimid; Zydus Pharmaceuticals Inc), and dexamethanose (VRd), for the treatment of patients with transplant-ineligible newly diagnosed (ND) multiple myeloma (MM).1 This decision is based on the positive results from the IMROZ phase 3 clinical study (NCT03319667), which measured the success of isatuximab in combination with VRd.1 If approved, this treatment would mark the first anti-CD38 therapy available in combination with VRd therapy for patients with NDMM.1-2

multiple myeloma blood cells

The ability of isatuximab to bind to CD38 enhances cytotoxicity of myeloma cells and modulates the tumor microenvironment, making cancer cells more susceptible to immune system attacks. Image Credits: © Marharyta - stock.adobe.com

MM affects more than 130,000 individuals in the United States, making it the second most common hematologic cancer with an estimated 32,000 diagnoses each year.3 In recent years, multiple studies have noted success in use of isatuximab in combination with standard-of-care therapies for patients. Positive results have been observed for populations who are relapsed or refractory (R/R) or are transplant ineligible.3-5 These findings have established isatuximab as a critical component of the standard-of-care treatment regimen for MM.

Isatuximab is a monoclonal antibody that targets CD38, which is found on the surface of malignant MM cells. When isatuximab binds to CD38, it helps the immune system identify and destroy cancerous cells through antibody-dependent, cell-mediated cytoxocity, as well as activation of natural killer cells, increased phagocytic activity of monoctyes, and complement dependent cytotoxicity. The ability of isatuximab to bind to CD38 enhances cytotoxicity of myeloma cells but also modulates the tumor microenvironment, making the cancer cells more susceptible to immune system attacks.6

In the global, randomized, multi-center, open-label IMROZ phase 3 clinical study, 466 patients with transplant-ineligible NDMM across 21 countries and 104 centers were administered isatuximab in combination with VRd. The primary endpoint was progression-free survival, with secondary endpoints of complete response, minimal residual disease negativity, very good partial response or better, and overall survival. Study authors also measured metrics such as overall response rates to treatment, including time to progression, duration of response, time to first response, time to best response, and safety.2

Patients received isatuximab intravenously at a dose of 10 mg/kg once per week for 5 weeks during a 42-day cycle and once every 2 to 4 weeks in combination with subcutaneous bortezomib, oral lenalidomide, and IV or oral dexamethasone. Following this initial treatment, patients were administered isatuximab for 28-day cycles in combination with lenalidomide and dexamethasone at the standard dose every 2 weeks from cycles 5 to 17 and every 4 weeks in cycles 18 and up.2

Isatuximab is currently approved for use in combination with pomalidomide and dexamethasone for the treatment of certain patients with R/R MM in >50 countries in the United States and Europe. Furthermore, the combination of isatuximab, carfilzomib (Kyprolis; Amgen Inc), and dexamethasone has been approved for use in patients with R/R MM, who have undergone 1 to 3 prior lines of therapy in the United States, and in patients with MM who have received at least 1 prior therapy in Europe.1

“Despite recent advancements in [MM] treatment, there remains a significant unmet need for new frontline therapies, particularly for transplant-ineligible patients, who can face poor outcomes from the disease,” said Dietmar Berger, MD, PhD, chief medical officer and global head of development at Sanofi, in a press release. “The filing acceptances, as well as the FDA’s Priority Review designation, reinforce our confidence in [isatuximab] as a potential best-in-class treatment and represent a critical step toward advancing this combination in a difficult-to-treat cancer.”1

1. Sarclisa accepted for FDA priority review for the treatment of transplant-ineligible newly diagnosed multiple myeloma. Press release. Sanofi. May 27, 2024. Accessed May 28, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-05-27-05-00-00-2888291
2. Sanofi. Clinical benefit of SAR650984, bortezomib, lenalidomide and dexamethasone combination in NDMM patients not eligible for transplant (IMROZ).ClinicalTrials.gov identifier:NCT03319667. Updated April 8, 2024. Accessed May 28, 2024. https://clinicaltrials.gov/study/NCT03319667
3. Pharmacist medication insights: isatuximab for multiple myeloma. Pharmacy Times. May 21, 2022. Accessed May 28. 2024. https://www.pharmacytimes.com/view/pharmacist-medication-insights-isatuximab-for-multiple-myeloma
4. Oncology overview: isatuximab-irfc (sarclisa) for relapsed/refractory multiple myeloma. Pharmacy Times. October 5, 2021. Accessed May 28, 2024. https://www.pharmacytimes.com/view/oncology-overview-isatuximab-irfc-sarclisa-for-relapsed-refractory-multiple-myeloma
5. Sarclisa combination shows positive results in patients with relapsed multiple myeloma. Pharmacy Times. May 18, 2022. Accessed May 28, 2024. https://www.pharmacytimes.com/view/sarclisa-combination-shows-positive-results-in-patients-with-relapsed-multiple-myeloma
6. Zhu C, Song Z, Wang A, et al. Isatuximab acts through fc-dependent, independent, and direct pathways to kill multiple myeloma cells. Front Immunol. 2020;11:1771. doi:10.3389/fimmu.2020.01771
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