Clinicians at the Second People's Hospital of Yibin, China, report the first documented case of hepatic pseudoprogression in a patient receiving bulumtatug fuvedotin (9MW2821), Mabwell's Nectin-4–targeting antibody-drug conjugate, according to a case report published in The New England Journal of Medicine in April 2026. The finding carries direct implications for how clinicians interpret imaging during ADC therapy.
The case involved a patient with metastatic cervical squamous-cell carcinoma refractory to platinum–taxane chemotherapy, with no prior immunotherapy history. After two cycles of 9MW2821 monotherapy, serum squamous cell carcinoma antigen levels fell from 37.0 ng/mL to 1.2 ng/mL, within the normal range of 1.5 ng/mL or below, and baseline metastatic lesions showed regression. CT imaging simultaneously revealed a new 1.8 cm × 2.5 cm hypoattenuating lesion in the medial segment of the left hepatic lobe. Liver biopsy showed dense infiltration of lymphocytes, plasma cells, and neutrophils, with no viable tumor cells, granulomas, spindle cell proliferation, or features consistent with inflammatory pseudotumor or sarcoid-like reaction. Treatment continued without interruption, the lesion resolved on subsequent imaging, and no recurrence was documented over two years of follow-up.
9MW2821 is a Nectin-4–targeting ADC in which an antibody directed against the cell adhesion molecule Nectin-4 delivers a cytotoxic payload upon receptor-mediated internalization. Nectin-4 is overexpressed across multiple solid tumor types, including cervical squamous cell carcinoma. The authors hypothesized that ADC-induced tumor cell death in this p16-positive patient, whose high HPV antigenicity may have primed an immune response, triggered release of damage-associated molecular patterns that recruited immune cells to a site of occult hepatic micrometastasis. That immune infiltration, rather than viable tumor, produced the radiographic lesion. Pseudoprogression of this type has been described in the context of PD-1 and PD-L1 checkpoint inhibitor therapy. Its occurrence during ADC monotherapy, without any concurrent immunotherapy, is characterized in the report as a globally unprecedented observation for this drug class in solid tumors.
The clinical management implication is direct. Had the treating team discontinued 9MW2821 based on imaging alone, the patient would have been removed from a regimen under which her disease was responding. The report argues that biopsy confirmation is warranted before classifying new lesions as progression during ADC therapy, particularly in patients with features that may predispose to immune activation such as p16 positivity and immunotherapy-naive status.