isatuximab — Drug Monograph

Brand names: Sarclisa, Sarclisa Escena

Drug class: Monoclonal Antibody

Mechanism of Action

Chimeric IgG1 anti-CD38 monoclonal antibody that binds a unique epitope on CD38 that is distinct from the daratumumab-binding site. Mechanism of action includes: (1) antibody-dependent cellular cytotoxicity (ADCC); (2) antibody-dependent cellular phagocytosis (ADCP); (3) complement-dependent cytotoxicity (CDC); (4) direct induction of apoptosis without requirement for cross-linking; and (5) immunomodulation via depletion of CD38-expressing immunosuppressive cells (regulatory T cells, regulatory B cells, myeloid-derived suppressor cells). Also inhibits the ectoenzyme cyclase and hydrolase…

FDA Indications

• Relapsed or refractory multiple myeloma in combination with pomalidomide and dexamethasone after ≥2 prior therapies including lenalidomide and a proteasome inhibitor (IV: FDA approval March 2020, ICARIA-MM: PFS HR 0.596; SC via on-body injector: FDA approval July 2026, IRAKLIA trial)
• Relapsed or refractory multiple myeloma in combination with carfilzomib and dexamethasone after 1–3 prior lines including lenalidomide (IV: FDA approval March 2021, IKEMA: PFS HR 0.531; SC via on-body injector: FDA approval July 2026, IZALCO trial)
• Newly diagnosed multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for patients not eligible for autologous stem cell transplant (SC via on-body injector: FDA approval July 2026, IsaSocut trial)

Common Side Effects

• Infusion-related reactions (38% in first infusion; mostly Grade 1–2)
• Neutropenia
• Fatigue
• Upper respiratory tract infection
• Pneumonia
• Diarrhea
• Nausea
• Thrombocytopenia

Clinical Pearl

As of July 2026, isatuximab is available in both IV (Sarclisa) and subcutaneous (Sarclisa Escena) formulations — the SC form is delivered via a wearable on-body injector in ~7 minutes, compared to a ~3-hour IV infusion. Isatuximab and daratumumab are both anti-CD38 antibodies but bind different CD38 epitopes. Both interfere with blood bank compatibility testing (indirect antiglobulin test/Coombs) due to CD38 on RBCs — blood bank must be notified and phenotyped RBCs or genotyping used for…

Related Therapies & Mechanisms

• Daratumumab (Darzalex) — Monoclonal Antibody · Myeloma
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