Clearly defining contraindications and principles for special populations is key to ensuring the safety of isatuximab therapy.

I. Absolute Contraindications

1. History of Severe Allergic Reactions

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

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

2. Pregnancy‑Related Combination Therapy Restrictions

(1) When used in combination with pomalidomide or lenalidomide, isatuximab is absolutely contraindicated in pregnant women because the latter two have established teratogenicity and embryotoxicity.

(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 Breastfeeding Women

(1) Based on its mechanism of action, this product may cross the placenta, causing fetal immune cell depletion and decreased bone 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 of childbearing potential must use effective contraception during treatment and for 7 months after the last dose.

3. Children and Adolescents

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

4. Elderly Patients (≥65 years)

(1) Elderly patients (especially those over 75 years) require enhanced monitoring during treatment.

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

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

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

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

III. Precautions for Co‑existing Conditions

1. Active Infection

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

(2) If a new infection occurs during treatment, the drug should be temporarily withheld and active anti‑infective management should be instituted.

2. Hepatic Impairment

Mild hepatic impairment does not significantly affect drug exposure, but 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 liver enzymes should be closely monitored.

3. Renal Impairment

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

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

4. Blood Transfusion and Blood Compatibility Interference

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

(2) It is recommended to complete blood type screening before treatment and to inform the blood transfusion service that the patient is receiving this drug.