Gastrointestinal and hepatobiliary toxicities associated with bispecific antibody therapy in hematologic malignancies: A retrospective single-center study.

Abstract

Abstract Background: Bispecific antibody (bsAb) therapies have revolutionized treatment of hematologic malignancies; however, gastrointestinal (GI) and hepatobiliary toxicities remain poorly studied in this population. Our aim was to assess the incidence, timing, and types of GI toxicities among bsAb-treated patients at the University of Oklahoma Health Sciences Center. Methods: We obtained IRB approval and conducted a single-center, retrospective study of adult patients who received bsAb therapies in the outpatient setting between July 2023 and April 2025 at Stephenson Cancer Center. Data on GI symptoms (nausea, vomiting, diarrhea, abdominal pain, dry mouth, taste disturbances, appetite changes), hepatic lab markers (AST, ALT, bilirubin, alkaline phosphatase), pancreatic enzymes, and stool studies were collected. Results: Among 48 patients, nausea (56.2%), decreased appetite (58.3%), and taste disturbances (31.2%) were most common reported symptoms. Diarrhea occurred in 22.9%, and abdominal pain in 27%, with variable etiologies. AST/ALT were elevated in 22.9% within 7 days of the first bsAb dose and in 54.2% throughout follow-up. Median baseline AST and ALT were 16.0 and 23.0, respectively. AST elevations had a median 81.0, with 4 cases >100, 1 >200, and 1 >500; ALT elevations had a median of 50.0, with 1 case >100 and none >200 or >500. Total bilirubin was elevated in 18.8%, direct bilirubin in 37.5%, and alkaline phosphatase in 27.1%, after receiving bsAb. PT/INR abnormalities occurred in 20.8% within 7 days and in 25% overall. GI bleeding was seen in 6.2% (hematochezia 4.2%, melena 2.1%). Gastritis was the most common diagnosis (n=6.2%), followed by hepatitis, colitis, diverticulitis, pancreatitis, and GI ischemia or obstruction (n= 4.2%). Gastroenteritis and drug-induced liver injury were noted in 2.1% each. No cases of cholecystitis, mesenteritis, pneumatosis, appendicitis, HBV/HCV reactivation, or liver failure occurred. GI consultations were obtained in 14.6%, often for persistent or complex symptoms. Conclusions: Our findings highlight the frequency and diversity of GI and hepatobiliary toxicities in patients receiving bsAb therapies. While many cases are mild, prolonged symptoms and diagnostic complexity are seen in a minority of patients and co management with gastrointestinal physicians is required to continue the bsAb in those patients.