New data from the GMMG-HD7 phase 3 trial reveals that Sarclisa (isatuximab), when combined with lenalidomide, bortezomib, and dexamethasone (RVd), significantly improves progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) who are eligible for transplant. This investigational combination demonstrates a clinically meaningful reduction in disease progression or death compared to RVd induction therapy alone, regardless of the maintenance regimen.
The GMMG-HD7 study, a two-part, double-randomized trial, enrolled 662 transplant-eligible NDMM patients across 67 sites in Germany. Participants were randomized to receive either Sarclisa plus RVd or RVd alone for three 42-day cycles. Following transplant, patients were re-randomized to receive Sarclisa plus lenalidomide or lenalidomide alone as maintenance therapy. Sarclisa was administered intravenously at 10 mg/kg weekly for the first four weeks of cycle one, then every other week for the remaining induction period.
Key Findings from the GMMG-HD7 Trial
The primary endpoint of the first part of the study was minimal residual disease (MRD) negativity after induction therapy. The key secondary endpoint was PFS from first randomization. MRD negativity was assessed using next-generation flow cytometry with a sensitivity of 1x10-5.
Hartmut Goldschmidt, MD, President of GMMG and Professor of Medicine at Heidelberg University Hospital, emphasized the importance of successful induction therapy in reducing relapse risk. "These data provide evidence that the Isa-RVd regimen potentially improves progression-free survival in the frontline, transplant-eligible population and supports the potential of this quadruplet to become a new standard-of-care induction regimen in this treatment setting," said Goldschmidt.
Sarclisa's Role in Multiple Myeloma Treatment
Sarclisa is a monoclonal antibody that targets the CD38 receptor on multiple myeloma cells, inducing antitumor activity through various mechanisms, including apoptosis and immunomodulation. CD38 is highly expressed on MM cells, making it an effective target for antibody-based therapies.
Dietmar Berger, MD, PhD, Chief Medical Officer and Global Head of Development at Sanofi, highlighted the study's design to understand the distinct effect of targeting CD38 with Sarclisa in induction versus maintenance treatment. "These data build upon our belief that Sarclisa has the potential to be a best-in-class CD38 therapy that could improve long-term outcomes versus the standard of care for certain patients," Berger stated.
Current Treatment Landscape and Future Directions
Multiple myeloma is the second most common hematologic malignancy, with over 180,000 new diagnoses worldwide annually. Despite available treatments, it remains incurable for most patients, with an estimated 61% five-year survival rate for newly diagnosed patients. Sanofi is committed to advancing Sarclisa through ongoing phase 3 clinical studies, exploring new combinations and methods of delivery, including subcutaneous administration, to improve patient outcomes across the MM treatment continuum.
The use of Sarclisa in combination with RVd is investigational and has not been evaluated by any regulatory authority.
