As a cytolytic antibody-drug targeting Claudin 18.2, zolbetuximab is used in the treatment of HER2-negative, CLDN18.2-positive locally advanced unresectable or metastatic adenocarcinoma of the stomach/gastroesophageal junction. The most common adverse reactions of zolbetuximab include gastrointestinal reactions, systemic reactions, and others.

Main Adverse Reactions of Zolbetuximab

1. Allergic Reactions

The incidence of allergic reactions during zolbetuximab treatment is 18%, among which severe (Grade 3-4) reactions account for 2%. Clinical manifestations include:

(1) Cutaneous manifestations: Urticaria, pruritus.

(2) Respiratory system: Recurrent cough, wheezing, feeling of laryngeal tightness/voice changes.

(3) Circulatory system: Hypertension, chest discomfort.

(4) Others: Fever, chills, back pain, increased salivation.

2. Infusion-Related Reactions

The incidence of infusion-related reactions is 3.2%, of which 0.4% are Grade 3 reactions. Management principles:

(1) Grade 2 reactions: Immediately interrupt the infusion; resume the infusion at a reduced rate after symptoms subside to Grade 1.

(2) Grade 3-4 reactions or allergic reactions: Permanently discontinue the drug and provide treatment according to standard medical measures.

(3) Subsequent prevention: After an allergic reaction occurs, pre-administer antihistamines before subsequent infusions.

3. Severe Nausea and Vomiting

Nausea (82%) and vomiting (67%) are the most common adverse reactions, with the highest incidence in the first cycle:

(1) Grade 3 nausea: Reaches 16% when combined with the mFOLFOX6 regimen, and 9% when combined with the CAPOX regimen.

(2) Grade 3 vomiting: Reaches 16% when combined with the mFOLFOX6 regimen, and 12% when combined with the CAPOX regimen.

(3) Key points of clinical management

a. Prophylactic medication:

Antiemetics (such as NK-1 receptor antagonists, 5-HT3 receptor antagonists) must be used in combination before each zolbetuximab infusion.

b. Graded management:

Grade 2: Pause the infusion until symptoms subside to ≤ Grade 1.

Grade 3: Pause drug administration until symptoms subside; adjust the infusion rate for subsequent doses.

Grade 4: Permanently discontinue the drug.

c. Supportive treatment: Fluid replacement and maintenance of electrolyte balance.

Detailed Description of Common Adverse Reactions of Zolbetuximab

1. Gastrointestinal Reactions

In addition to nausea and vomiting, other common gastrointestinal reactions of zolbetuximab include:

(1) Diarrhea: Incidence is approximately 35-45%, with Grade 3 accounting for about 2.9%.

(2) Abdominal pain: Incidence is approximately 20-25%.

(3) Constipation: Incidence is approximately 18-20%.

(4) Decreased appetite: Incidence is approximately 41-47%, with Grade 3 accounting for about 6-7%.

2. Systemic Reactions

(1) Fatigue: Incidence is approximately 35-40%.

(2) Fever: Incidence is approximately 15-18%.

(3) Peripheral edema: Incidence is approximately 18-20%.

3. Neurological Reactions

(1) Peripheral sensory neuropathy: Incidence is approximately 20-25%.

(2) Headache: Incidence is approximately 10-15%.

Laboratory Abnormalities of Zolbetuximab

1. Hematological Abnormalities

(1) Neutropenia: Incidence is 76%, with Grade 3-4 reaching 21%.

(2) Leukopenia: Incidence is 66%, with Grade 3-4 reaching 6-8%.

(3) Anemia: Incidence is approximately 45-50%, with Grade 3-4 reaching 10-15%.

(4) Thrombocytopenia: Incidence is approximately 20-25%, with Grade 3-4 reaching 3-7%.

2. Biochemical Index Abnormalities

(1) Hypoalbuminemia:

Incidence is 66-78%, with Grade 3-4 reaching approximately 3-4.4%.

(2) Electrolyte disturbances:

a. Hypokalemia: Incidence is 28%, with Grade 3-4 reaching 11%.

b. Hyponatremia: Incidence is 29%, with Grade 3-4 reaching 5%.

c. Hypomagnesemia: Incidence is approximately 15-20%.

(3) Liver function abnormalities:

a. Increased AST: Incidence is approximately 25-30%.

b. Increased ALT: Incidence is approximately 20-25%.

c. Increased alkaline phosphatase: Incidence is approximately 15-20%.

(4) Renal function abnormalities:

The incidence of increased creatinine is approximately 35-40%.

The management of zolbetuximab-related adverse reactions requires multidisciplinary collaboration. Through prophylactic medication, close monitoring, and timely intervention, most patients can successfully complete treatment. During clinical use, the benefits and risks should be fully weighed, and individualized treatment plans should be developed.