Addition of Isatuximab to RVd as Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma (GMMG-HD7)

Background

• Lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd) is a recommended, preferred first regimen in transplant-eligible newly diagnosed multiple myeloma (NDMM). Maximizing treatment response before transplant is important for patient outcomes
• The NDMM landscape is evolving rapidly and regimens incorporating anti-CD38 monoclonal antibodies are becoming the new standard of care in patients eligible for autologous stem cell transplantation (ASCT)
• Isatuximab targets a specific epitope on CD38, a transmembrane glycoprotein widely and uniformly expressed on myeloma cells. It is approved in several countries in combination with dexamethasone plus either pomalidomide or carfilzomib in adult patients with relapsed/refractory multiple myeloma who have received prior therapies
• GMMG-HD7 is the first phase 3 study to evaluate minimal residual disease (MRD) negativity at the end of induction in transplant-eligible NDMM patients comparing isatuximab-RVd with RVd

Methods

• GMMG-HD7 is a phase 3 clinical trial where the primary end point is MRD negativity at the end of the induction phase
• 662 patients were enrolled; 1:1 randomization at induction and randomization at maintenance
• The study population included patients aged 18-70 years old with NDMM who were eligible for high-dose therapy and ASCT
• Baseline patient characteristics were generally balanced between both arms

Results

• First primary end point, end of induction MRD negativity by NGF (10-5), was met in intention-to-treat analysis
  • Isatuximab-RVd is the first regimen to demonstrate a rapid and statistically significant benefit from treatment by reaching a MRD negativity of 50.1% at the end of induction and to show superiority vs RVd in a phase 3 trial
  • There was consistent end-of-induction MRD negativity benefit of isatuximab-RVd across all subgroups
  • The study is ongoing following the second randomization for maintenance
• Although the rates of complete response after induction therapy did not differ between the isatuximab-RVd and RVd arms, there was a significant increase in ≥VGPR (very good partial response) rates and overall response rate with isatuximab-RVd
• Addition of isatuximab to RVd had limited effect on safety profile. A comparable number of patients discontinued induction therapy because of adverse events in the isatuximab-RVd arm vs RVd arm
• Addition of isatuximab did not affect RVd dose intensity
• Isatuximab is currently being investigated in other phase 3 studies for the treatment of transplant-eligible and -ineligible NDMM in combination with RVd as well as with carfilzomib, lenalidomide, and dexamethasone (KRd)