Isatuximab Receives FDA Approval for First-Line Treatment of Transplant-Ineligible Multiple Myeloma

On September 20, 2024, the United States Food and Drug Administration (FDA) approved treatment for adults who are ineligible for autologous stem cell transplantation and have newly diagnosed multiple myeloma: isatuximab-irfc (Sarclisa, Sanofi-Aventis) in combination with bortezomib, lenalidomide and dexamethasone.

Multiple myeloma (MM) is a difficult-to-treat cancer that originates in plasma cells. Treatment options remain limited, particularly for patients who are ineligible for autologous stem cell transplantation. Isatuximab (Sarclisa) is an anti-CD38 antibody previously approved for use in advanced multiple myeloma. The FDA has now expanded the drug's label to approve its use in combination with bortezomib, lenalidomide and dexamethasone (the VRd regimen) in patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation. This marks an important milestone in multiple myeloma treatment and may improve patients' survival by expanding their treatment options. The approval offers a new alternative to treatments previously used in a similar indication with daratumumab (Darzalex).

Sarclisa Approval: The IMROZ Study and Its Results

Sarclisa's new approval is based on IMROZ, an open-label phase 3 clinical trial. In this study, 446 patients with multiple myeloma who were ineligible for autologous stem cell transplantation were randomly assigned to two groups: 60% were treated with isatuximab and the VRd regimen, while 40% received placebo and the VRd regimen.

After a median follow-up of 59.7 months, 63.2% of patients in the group receiving added Sarclisa were alive without disease progression, compared with 45.2% in the placebo group.

Median progression-free survival (PFS) had not yet been reached in the Sarclisa group, compared with 54.3 months in the placebo group. Statistical analyses showed that Sarclisa reduced the risk of disease progression by 40% (HR, 0.60; 98.5% CI, 0.41-0.88; P < 0.001).

These results show that Sarclisa provides substantial additional benefit beyond existing standards of care for patients with multiple myeloma who are ineligible for autologous stem cell transplantation. Sanofi's press release emphasized that IMROZ was the first global phase 3 trial combining anti-CD38 monoclonal antibodies with the VRd regimen. This represents a critical innovation in diversifying treatment options.

How Does Sarclisa Work?

Sarclisa, whose active ingredient is isatuximab, is a monoclonal antibody that targets multiple myeloma cells by binding to the CD38 protein. CD38 is expressed at high levels on the surface of myeloma cells and helps the immune system recognize these cells. This binding both activates the cellular immune response and accelerates cell death.

Side Effects and Safety Profile

The most common side effects in the isatuximab arm of IMROZ included upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataracts, constipation, peripheral edema, skin rash, infusion reactions and insomnia. These side effects were observed in more than 20% of patients. COVID-19 infection was also among the reported side effects.

Another notable finding was that 11% of patients in the Sarclisa group died during treatment. This rate was significantly higher than the 5.5% in the placebo group and was mostly associated with deaths due to infections. This suggests that patients receiving Sarclisa require closer monitoring for infection risk.

Dosage and Cost

Sarclisa is administered at a dose of 10 mg/kg weekly for the first 4 weeks, then every 2 weeks until disease progression or unacceptable toxicity occurs. The reported cost of the drug is 30298.01 Turkish lira for 500 mg / 25 ml.

Conclusion: New Horizons in Multiple Myeloma Treatment

The approval of Sarclisa in combination with the VRd regimen as first-line treatment for patients with multiple myeloma who are ineligible for autologous stem cell transplantation is considered a major advance for this patient group. Clinical trial results show a significant increase in patients' progression-free survival. However, the side effects observed during treatment and the increased risk of infection require vigilance from the doctors administering it. Sarclisa offers an important alternative to other anti-CD38 antibodies such as daratumumab and contributes to the development of personalized approaches to multiple myeloma treatment. This innovative treatment option offers new hope in addressing the challenges of treating multiple myeloma.