The landscape of multiple myeloma treatment has undergone a profound transformation with the advent of monoclonal antibodies (mAbs) targeting CD38. Among the notable breakthroughs, two anti-CD38 mAbs, DARZALEX (daratumumab) and SARCLISA (isatuximab-irfc), have been approved for clinical use. These groundbreaking multiple myeloma therapies are a game-changer, offering a fresh and effective approach for newly diagnosed multiple myeloma (NDMM) patients and relapsed/refractory multiple myeloma (R/R MM).

SARCLISA (targets a unique epitope on CD38, a transmembrane glycoprotein that is widely and uniformly expressed on myeloma cells. SARCLISA is being evaluated in the Transplant-Ineligible newly Diagnosed Multiple Myeloma (GMMG-HD7 study) in addition to IMROZ study in Transplant-Ineligible newly Diagnosed Multiple Myeloma.

The GMMG-HD7 trial is the first phase III study to assess minimal residual disease (MRD) negativity at the end of induction in transplant-eligible NDMM patients by comparing isatuximab-RVd with RVd. The GMMG-HD7 trial led by Hartmut Goldschmidt from Germany looked at a very large number of newly diagnosed patients.

In previously reported results from the GMMG-HD7 trial, among patients who per protocol remained in the study, the MRD negativity rates at the end of intensification were 72.0% (219 of 304 patients) after Isa-RVd and 56.5% (157 of 278 patients) following RVd (OR 1.98, 95% CI 1.39; 2.85). MRD assessment at the end of intensification was unavailable for 17 and 10 patients, respectively.

Sanofi presented updated interim results in EHA 2024 from this ongoing GMMG-HD7 trial. 

• MRD negativity status after induction with Isa-RVd vs. RVd was confirmed in 85.9% vs. 82.6% after intensification of Isa-RVd.

• Only 6/9 patients, respectively, lost their MRD negative status.

• 66 vs. 56 patients (52.8%/36.8%) converted from MRD positive after induction to MRD negative after intensification.

582 patients completed at least one high-dose therapy (HDT)/ASCT: 304 (91.8%) after Isa-RVd; 278 (84.5%) after RVd. 179 patients received a second HDT/ASCT: 80 (26.3%) after Isa-RVd: 99 (35.6%) after RVd.

KOL insights

“The GMMG-HD7 study showed that Isatuximab combined with RVd induction in transplant-eligible NDMM patients increased MRD negativity rates post-HDT/ASCT without affecting RVd's safety or intensity. GMMG-HD7 continues, exploring isatuximab with lenalidomide in maintenance, promising enhanced CR and MRD outcomes.” – MD, United States

“Many investigators and clinicians are still unsure if continued use of daratumumab (or another anti-CD38 monoclonal antibody) in maintenance is necessary, and this study did not answer that question. Many of us do not routinely use daratumumab in maintenance, except in high-risk patients. Additional ongoing studies including the SWOG S1803 study and the GMMG-HD7 study will answer that important question.” – MD, United States

Conclusion 

Market presence in frontline settings is essential from a business perspective because of the high patient base and less emerging competition. In 2025, based on findings from the phase III GMMG-HD7 study, Sanofi is anticipating possible regulatory filing for SARCLISA-VRd in first-line transplant eligible myeloma patients. In the latter part of 2024, the final data readout is anticipated. SARCLISA is expected to compete with DARZALEX in this setting as well.  Data from PERSEUS study also presented at EHA, and the data further highlight the benefit of D-VRd and D-R maintenance as a new standard of care for transplant-eligible patients with NDMM. Janssen has already filed the sBLA in the US and EU for transplant-eligible patients with NDMM. DARZALEX-VRd combo has the benefit of being the first mover in this setting. 

The GMMG-HD7 trial is ongoing and aims to further evaluate the role of the anti-CD38 monoclonal antibody isatuximab in combination with lenalidomide following a second randomization at the start of the maintenance phase. The addition of isatuximab to RVd induction therapy has been shown to improve both CR and MRD negativity rates after HDT and ASCT, highlighting its potential to enhance treatment outcomes for patients with NDMM.