July 9, 2026
The U.S. Food and Drug Administration (FDA) has approved subcutaneous isatuximab-irfc (Sarclisa Escena, Sanofi)for multiple myeloma, introducing a more convenient method of delivering anti-CD38 immunotherapy while maintaining efficacy comparable to the intravenous formulation.
The approval expands the use of subcutaneous isatuximab across both newly diagnosed and relapsed multiple myeloma, reflecting the ongoing shift toward patient-friendly immunotherapy administration without compromising clinical outcomes.
Multiple Myeloma: Symptoms, Causes, Stages, Diagnosis and Treatment
Approved Indications
Subcutaneous isatuximab-irfc is approved in combination with:
- Pomalidomide + dexamethasone (Isa-Pd) for adults with multiple myeloma who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor.
- Carfilzomib + dexamethasone (Isa-Kd) for patients with relapsed or refractory multiple myeloma after one to three prior therapies.
- Bortezomib, lenalidomide, and dexamethasone (Isa-VRd) for newly diagnosed transplant-ineligible patients.
These indications mirror the approved intravenous formulation while offering a simplified subcutaneous route of administration.
Clinical Evidence
IRAKLIA: Non-Inferiority to Intravenous Isatuximab
The pivotal IRAKLIA phase III study enrolled 531 patients with relapsed or refractory multiple myeloma receiving isatuximab plus pomalidomide and dexamethasone.
Patients were randomized to receive either subcutaneous or intravenous isatuximab. The study successfully demonstrated non-inferiority of the subcutaneous formulation.
Overall response rates were virtually identical:
- 71.1% with subcutaneous isatuximab
- 70.5% with intravenous isatuximab
In addition, pharmacokinetic analyses showed higher steady-state trough drug concentrations with the subcutaneous formulation, confirming adequate systemic exposure.
IZALCO
The phase II IZALCO study evaluated subcutaneous isatuximab combined with carfilzomib and dexamethasone in patients with relapsed or refractory disease.
The regimen achieved an impressive overall response rate of 79.7%, supporting its use in earlier relapse settings.
IsaSocut
The investigator-sponsored phase II IsaSocut trial evaluated subcutaneous isatuximab combined with VRd in patients with newly diagnosed transplant-ineligible multiple myeloma.
The study demonstrated exceptionally high activity, with an overall response rate of 97.3%, highlighting the strong efficacy of CD38-targeted immunotherapy in frontline treatment.
Safety Profile
The safety profile of subcutaneous isatuximab remained consistent with the established intravenous formulation.
The prescribing information includes warnings regarding:
- hypersensitivity and administration-related reactions,
- neutropenia,
- infections,
- secondary primary malignancies,
- laboratory test interference,
- embryo-fetal toxicity.
No new safety concerns were identified with subcutaneous administration.
Why This Approval Matters
CD38 monoclonal antibodies have become a cornerstone of multiple myeloma therapy. The availability of a subcutaneous formulation represents another important step toward improving patient experience while maintaining clinical efficacy.
Compared with intravenous administration, subcutaneous delivery has the potential to reduce treatment time, simplify clinic workflows, and improve patient convenience without sacrificing therapeutic benefit.
Following the success of subcutaneous daratumumab, this approval further expands the trend toward more accessible antibody-based immunotherapy for patients with multiple myeloma.
Conclusion
The FDA approval of subcutaneous isatuximab-irfc provides a new administration option for anti-CD38 immunotherapy across multiple stages of multiple myeloma. Supported by the phase III IRAKLIA trial and complementary phase II studies, the subcutaneous formulation demonstrated efficacy comparable to intravenous isatuximab while offering a more convenient treatment approach. As immunotherapy continues to evolve in hematologic malignancies, this approval represents another meaningful advance in optimizing both treatment effectiveness and patient-centered care.