First-line induction therapy with Sarclisa delays myeloma progression

Adding Sarclisa (isatuximab) to standard induction therapy for transplant-eligible people with newly diagnosed multiple myeloma extends the time patients live without their disease progressing, regardless of the maintenance regimen they subsequently receive.

That’s according to the latest data from the Phase 3 GMMG-HD7 clinical trial (NCT03617731), which is testing Sarclisa when added to a standard induction regimen and/or post-transplant maintenance therapy in more than 650 transplant-eligible myeloma patients, all of whom were newly diagnosed and not yet receiving treatment.

Standard induction treatment consisted of Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone, known as RVd, and post-transplant maintenance therapy using Revlimid.

“Sarclisa has the potential to be a best-in-class CD38 [inhibitor] therapy that could improve long-term outcomes versus the standard-of-care for certain patients,” Dietmar Berger, MD, PhD, the chief medical officer and global head of development at Sanofi, which markets Sarclisa, said in a company press release.

Sanofi expects to present the study’s complete data at a future medical meeting.

“We look forward to the full data presentation and continuing our mission of helping make a meaningful difference for people living with multiple myeloma,” Berger said.

Investigating the use of Sarclisa in induction therapy

Hartmut Goldschmidt, MD, the trial’s principal investigator, said “these data provide evidence that the [Sarclisa-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.”

Health authorities in the U.S. and the European Union are reviewing a request for approval of Sarclisa’s use in combination with the RVd induction regimen in newly diagnosed multiple myeloma patients who are not eligible for transplant.

“Successful induction therapy is one of the most critical components to reduce the relapse or recurrence risk in patients with newly diagnosed multiple myeloma,” said Goldschmidt, also a professor of medicine at the Heidelberg University Hospital in Germany.

Multiple myeloma is a cancer of plasma cells, a type of white blood cells found in the bone marrow. Plasma cells usually help fight infections by producing antibodies. But in multiple myeloma, plasma cells multiply uncontrollably and produce abnormal antibodies, leading to bone damage and other symptoms.

Despite approved therapeutic options, multiple myeloma often relapses, meaning the cancer comes back after treatment or a period of remission in which no symptoms occur. For many patients, multiple myeloma is relapsed or refractory, meaning it stopped responding to treatment or never responded adequately.

Given by infusion into the bloodstream, Sarclisa works by blocking the CD38 protein, which is found in large amounts on the surface of myeloma cells. This not only directly destroys myeloma cells but also exposes them to elimination by the immune system, making it difficult for myeloma cells to survive.

Over 600 newly diagnosed patients took part in GMMG-HD7 study

The two-part GMMG-HD7 trial is testing the use of Sarclisa as part of first-line therapy in patients who are eligible for an autologous stem cell transplant, a procedure that uses a patient’s own stem cells to restore the body’s ability to produce healthy blood cells in the bone marrow.

“The GMMG-HD7 study was designed to better understand the distinct effect of targeting CD38 with Sarclisa in induction versus maintenance treatment of transplant-eligible patients,” Berger said.

In its first part, 662 participants were randomly assigned to receive three 42-day cycles of RVd induction regimen either alone or combined with Sarclisa, given once weekly in the first cycle and every other week in the following cycles.

The main goal was to assess the proportion of patients reaching minimal residual disease (MRD) negativity, which refers to the absence of a very small number of myeloma cells that can remain in the body after therapy and trigger future cancer relapse or progression.

The GMMG-HD7 study was designed to better understand the distinct effect of targeting CD38 with Sarclisa in induction versus maintenance treatment of transplant-eligible patients.

Previously published results from the first part showed that after 18 weeks, or about four months, a significantly greater proportion of patients on the Sarclisa combo achieved MRD negativity relative to those on RVd alone (50% vs. 36%). This reflected an 82% greater chance of meeting MRD negativity with Sarclisa.

“While we observed this investigational combination showed improved minimal residual disease negativity rates in the bone marrow, indicating potentially deeper responses after induction, further follow-up was needed to better understand how this translated to long-term outcomes,” Goldschmidt said.

In the trial’s second part, participants who completed induction treatment and subsequently received a transplant were randomly assigned to receive maintenance therapy with Revlimid, either with or without Sarclisa.

This part’s main goal was to assess progression-free survival (PFS), or the time patients lived without disease progression. PFS was measured from the second randomization to cancer progression or death from any cause, whichever came first, for up to three years.

Newly announced data demonstrated that adding Sarclisa to standard RVd induction treatment resulted in statistically significant and clinically meaningful improvements in PFS compared with RVd alone, regardless of whether patients received Sarclisa during subsequent maintenance therapy.