Sarclisa

Multiple myeloma — in combination with pomalidomide and dexamethasone, for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor; in combination with carfilzomib and dexamethasone, for relapsed or refractory after one to three prior lines of therapy

With pomalidomide + dex (28-day cycle): 10 mg/kg IV weekly for Cycle 1 (Days 1, 8, 15, 22), then every 2 weeks (Days 1, 15) starting Cycle 2
With carfilzomib + dex: Same dosing schedule
First infusion: 25 mL/h initial rate; may increase to max 150 mL/h
Pre-medication (30-60 min prior): Dexamethasone 40 mg (IV or PO), acetaminophen 650-1000 mg, diphenhydramine 25-50 mg (or equivalent), ranitidine 50 mg IV or equivalent

Injection: 20 mg/mL in 25 mL (500 mg) single-dose vial

None listed.

• Infusion-Related Reactions: 38.2% (Grade ≥3: 1.4%). Almost all (98.2%) occur during first infusion. Pre-medicate. For Grade 1-2: interrupt and resume at 50% rate. For Grade 3: stop and manage; may restart at 50% rate after complete resolution. For Grade 4: permanently discontinue.
• Neutropenia: 46% (Grade 3-4: 35%). Monitor CBCs periodically. Withhold for ANC <1.0 × 10⁹/L.
• Second Primary Malignancies: Monitor for development.
• Laboratory Test Interference: Anti-CD38 antibody may be detected on indirect antiglobulin test (Coombs). Type and screen before treatment. Interference with serum protein electrophoresis and immunofixation (may cause false positive M-protein).
• Embryo-Fetal Toxicity

Infusion-related reactions (38%), neutropenia (46%), upper respiratory tract infection (28%), pneumonia (23%), diarrhea (26%), fatigue (20%), nausea (15%)

Infusion reactions in 46% (Grade 3+ in 2%). Most occur during first infusion. Pre-medicate with dexamethasone, acetaminophen, H2 blocker, diphenhydramine. Grade 3+ neutropenia in 46%.

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Infusion reactions in 46% (Grade 3+ in 2%). Most occur during first infusion. Pre-medicate with dexamethasone, acetaminophen, H2 blocker, diphenhydramine. Grade 3+ neutropenia in 46%.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Isatuximab is a chimeric IgG1κ monoclonal antibody that binds to a specific extracellular epitope on CD38, a transmembrane glycoprotein abundantly expressed on multiple myeloma cells. It induces tumor cell death through multiple mechanisms: complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and direct apoptosis via Fc-independent crosslinking. Unlike daratumumab, isatuximab can also trigger apoptosis without external crosslinking agents.

Half-life: approximately 28 days. Clearance: 10.6 mL/h (decreases over time as CD38+ cells depleted). Vd: 8.0 L. Steady-state by approximately Cycle 4 (q2w). Linear PK at 10 mg/kg.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• ICARIA-MM — Isatuximab + pomalidomide/dex vs. pomalidomide/dex in relapsed/refractory MM. Phase III, n=307.
  🔬 NCT02990338 ↗ 📄 Primary Publication ↗

Sarclisa has FDA-approved indications across the following cancer types covered on PipelineEvidence: