Clear contraindications and principles for special populations are critical to ensuring the safety of isatuximab therapy.

I. Absolute Contraindications

1. History of Severe Allergic Reactions

(1) Isatuximab is contraindicated in patients with a history of severe allergy to isatuximab or any of its excipients (e.g., histidine, sucrose, polysorbate, etc.).

(2) Patients who have experienced severe systemic reactions to this product or other CD38 monoclonal antibodies in the past must not be re‑administered.

2. Pregnancy‑Related Combination Therapy Restrictions

(1) When isatuximab is combined with pomalidomide or lenalidomide, the latter two have well‑established teratogenicity and embryo‑fetal toxicity; therefore, this combination is absolutely contraindicated in pregnant women.

(2) Women of childbearing potential must have a negative pregnancy test before starting combination therapy.

II. Special Populations Requiring Caution or Evaluation

1. Pregnant and Lactating Women

(1) Based on its mechanism of action, isatuximab may cross the placenta, causing fetal immune cell depletion and reduced bone mineral density.

(2) During pregnancy, the potential risks should be explained, and use should be considered only if the benefit clearly outweighs the fetal risk.

(3) Because IgG can enter breast milk, breastfeeding should be discontinued during treatment and for 7 months after the last dose.

2. Contraceptive Requirements for Women of Childbearing Potential

Women with reproductive capacity must use effective contraception during treatment and for 7 months after the last dose.

3. Pediatric and Adolescent Patients

The safety and efficacy of isatuximab in pediatric patients have not been established; use is not recommended in individuals under 18 years of age.

4. Elderly Patients (≥65 years)

(1) In elderly populations (especially those ≥75 years), enhanced monitoring is required.

(2) Although overall efficacy is similar to that in younger patients, the risks of serious adverse events, fatal events, and severe infections increase with age. A comprehensive assessment of underlying diseases and organ function should be performed before treatment.

5. Patients with Cardiac Dysfunction (when combined with carfilzomib)

(1) When isatuximab is combined with carfilzomib, the risk of heart failure may be increased.

(2) In patients with a history of heart failure, cardiomyopathy, or hypertension, cardiac function should be evaluated before treatment, and symptoms such as dyspnea and edema should be monitored during therapy.

III. Precautions for Coexisting Conditions

1. Active Infection

(1) In the presence of active severe infections (e.g., pneumonia, sepsis), treatment should be delayed until the infection is controlled.

(2) If a new infection occurs during treatment, isatuximab should be temporarily withheld and appropriate anti‑infective therapy should be initiated.

2. Hepatic Impairment

Mild hepatic impairment does not significantly affect drug exposure; however, the pharmacokinetics in moderate‑to‑severe hepatic impairment (total bilirubin >1.5× upper limit of normal) are not established. Such patients should be treated with caution and closely monitored for changes in liver enzymes.

3. Renal Impairment

(1) Renal impairment (including end‑stage renal disease and dialysis patients) does not significantly affect isatuximab exposure, and no dose adjustment is required.

(2) However, the concomitant agents lenalidomide and pomalidomide require dose adjustments based on renal function; refer to their respective prescribing information.

4. Interference with Transfusion and Blood Compatibility

(1) Isatuximab may interfere with blood typing and cross‑matching tests (indirect antiglobulin test), affecting transfusion safety.

(2) Blood type screening should be performed before treatment, and the transfusion service should be informed that the patient is receiving this drug.