Abstract
BackgroundThe treatment of recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) remains challenging. Preclinical studies revealed that B cell depletion could modulate the microenvironment and overcome chemoresistance. We conducted a phase I study to evaluate the feasibility and safety of B cell depletion using the anti-CD20 antibody rituximab to treat HNSCC.MethodsTen patients were enrolled in two protocols. The first four patients treated using protocol 1 received rituximab 1000 mg on days −14 and −7, followed by gemcitabine/cisplatin every 3 weeks, and rituximab was administered every 6 months thereafter. Because of disease hyperprogression, protocol 1 was amended to protocol 2, which consisted of the concomitant administration of rituximab 375 mg/m2 and gemcitabine/cisplatin every 3 weeks. Another six patients were enrolled and treated using protocol 2.ResultsThree patients treated using protocol 1 exhibited rapid disease progression, and the remaining patient could not undergo evaluation after rituximab treatment. Conversely, no unpredicted harm was observed in the six patients treated using protocol 2. Among these patients, one achieved complete response, and two had partial responses. The disease-free durations in these patients were 7.0, 6.2, and 7.1 months, respectively. Immune cell analysis revealed a higher ratio of cytotoxic T cells to regulatory T cells in responders than in non-responders.ConclusionsB cell depletion using rituximab alone in patients with HNSCC can cause hyperprogressive disease. Contrarily, the co-administration of rituximab and cisplatin/gemcitabine was feasible and safe.Trial registrationClinicalTrials.gov Identifier: NCT04361409, 24 April 2020, retrospectively registered
Highlights
The treatment of recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) remains challenging
The development of programmed death 1 (PD-1) immune checkpoint inhibitors changed the treatment of HNSCC
All patients had measurable diseases as defined as the presence of at least one lesion as being ≥10 mm in at least one dimension measured with conventional computed tomography (CT) or ≥10 mm in at least one dimension measured with spiral CT scan or magnetic resonance imaging (MRI)
Summary
The treatment of recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) remains challenging. We conducted a phase I study to evaluate the feasibility and safety of B cell depletion using the anti-CD20 antibody rituximab to treat HNSCC. Recurrent or metastatic squamous-cell carcinoma of the head and neck (R/M HNSCC) has a dismal prognosis [1]. Systemic therapies such as chemotherapy or targeted therapy against EGFR have been the mainstay of palliation [2], but long-term disease control is difficult. Less than 20% of patients respond to this treatment, and the median progressionfree survival is approximately 5 months. Novel therapies are urgently required for patients with R/M HNSCC
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