Isatuximab (Sarclisa; Sanofi) in combination with standard-of-care significantly improved progression-free survival in patients with newly diagnosed multiple myeloma.
Isatuximab (Sarclisa; Sanofi) in combination with standard-of-care (SOC) lenalidomide (Revlimid; Bristol Myers Squibb), bortezomib (Velcade; Millennium Pharmaceuticals), and dexamethasone (Decadron; Pfizer) (VRd) during 18-week induction treatment followed by transplant demonstrated clinically meaningful improvements in progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (MM), according to data from the German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study (NCT03617731). The results have significant implications for using isatuximab as a foundational therapy in current SOC protocols, marking a notable advancement in the continually evolving landscape of MM treatment.1
MM is the second most common hematological malignancy affecting over 130,000 individuals in the United States, with an estimated 32,000 additional diagnoses each year. Over the past decade, the advent of advanced immunotherapies has been crucial for the safe and efficacious treatment of patients with MM. The discovery of the wide range of highly expressed targets on the surface of malignant cells led to the development of proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies, such as isatuximab.2,3
Isatuximab specifically targets and binds to CD38, a highly expressed protein found on the surface of myeloma cells. It helps the immune system identify and eliminate abnormal cells through antibody-dependent, cell-mediated cytoxocity, as well as activation of natural killer cells, increased phagocytic activity of monoctyes, and complement dependent cytotoxicity. Further, isatuximab can modulate the tumor microenvironment to make myeloma cells more susceptible to immune system attacks.2,3
In recent years, isatuximab has shown significant improvements in minimal residual disease (MRD) negativity and PFS when used with the current SOC regimens, including VRd, across various studies. Notably, the IMROZ phase 3 clinical study (NCT03319667) produced positive results, which led to the FDA granting isatuximab in combination with VRd priority review in May 2024.2-4
The positive initial results from the GMMG-HD7 phase 3 study further support prior clinical evidence demonstrating the capabilities of isatuximab in combination with VRd regimens. The randomized, open-label, multicenter, 2-part phase 3 study included 662 patients with transplant-eligible newly diagnosed MM across 67 sites in Germany. The patients were equally randomized to receive 3 42-day cycles of VRd that was administered intravenously at a dose of 10 mg/kg once weekly for the first 4 weeks of cycle 1 and then every other week for the remainder of the induction period. Post transplant, treatment was re-randomized for patients, who received either isatuximab plus lenalidomide or lenalidomide as maintenance therapy.5
Title: Trial on the Effect of Isatuximab to Lenalidomide/Bortezomib/Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7)
ClinicalTrials.gov ID: NCT03617731
Sponsor: University of Heidelberg Medical Center
Completion Date (Estimated): December 2025
The primary end point of the study was MRD after induction period in the first part of the study, which was assessed using next-generation flow cytometry (sensitivity of 1x10-5), and PFS. Additionally, secondary end points included rates of complete response after induction and intensification, overall survival, and safety. In the second part of the study defined PFS as the primary endpoint after transplant and re-randomization.5
The study results demonstrated a significantly improved PFS amongst patients who received isatuximab plus VRd compared with VRd alone, further reinforcing its potential as a foundational addition to the current SOC in the frontline. Despite expanding therapeutic options for newly diagnosed MM, outcomes typically decline with each successive line of therapy, underscoring the need for continual advancements to slow disease progression and improve patient outcomes.
“The GMMG-HD7 study was designed to better understand the distinct effect of targeting CD38 with [isatuximab] in induction versus maintenance treatment of transplant-eligible patients,” Dietmar Berger, MD, PhD, chief medical officer and global head of development at Sanofi, said in a news release. “We look forward to the full data presentation and continuing our mission of helping make a meaningful difference for people living with multiple myeloma.”5
