Tislelizumab Rechallenge for Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC) Previously Treated with Another Anti-PD1 Antibody

Abstract

<h3>Purpose/Objective(s)</h3> To explore the ORR and PFS of Tislelizumab rechallenge in combination with chemotherapy or stereotactic body radiation therapy (SBRT) for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) previously treated with another anti-PD1 antibody. <h3>Materials/Methods</h3> This was part of a prospective study. RM-NPC patients who showed no response to or progressed after PD-1 blockade were rechallenged with Tislelizumab plus chemotherapy or SBRT. Tislelizumab was given at a fixed dose of 200 mg, repeated every three weeks. Chemotherapy regimen was low dose gemcitabine plus metronomic capecitabine. SBRT was given 4 Gy to 6 Gy in three or five fractions depending on the tumor site. Tislelizumab was delivered one day after the completion of SBRT. The primary endpoint was the ORR. The secondary endpoints included PFS, duration of response (DoR), and safety. Dynamic assessment of T lymphocytes, B lymphocytes, natural killer (NK) cells (TBNK), and regulatory T cells (Tregs) from peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry every 2-3 months in order to analyze the change patterns following PD-1 blockade. <h3>Results</h3> From March 2019 to February 2022, 25 patients were enrolled in this study. All have previously received high dose platinum-based chemotherapy and PD-1 blockade. The salvage regimen was Tislelizumab rechallenge plus chemotherapy in 21 cases, and Tislelizumab plus SBRT in 4 cases. Altogether, there were 5 (20%) complete response (CR) and 12 (48%) partial response (PR), respectively. Stable disease (SD) and progressive disease (PD) were defined in 5 (20%) and 3 (12%) cases, respectively. The ORR was 17 out of 25 (68%). The disease control rate (DCR) was 22 out of 25 (88%). With a median follow-up of 12 months (4–26 months), three patients terminated immunotherapy due to disease progression, and the remaining 22 patients were still under treatment. The 1-year PFS was 78%, neither the median PFS nor the median DoR has been reached. Of the 12 patients who had regular TBNK and Treg surveillance in PBMCs, all showed an increasing trend in Treg accompanying with tumor progression. On the contrary, responders to Tislelizumab rechallenge demonstrated decrease of Treg in PBMCs. However, no specific regularity could be defined in TBNK. All observed adverse events during Tislelizumab rechallenge were defined as ≤ Grade 2. <h3>Conclusion</h3> Tislelizumab rechallenge combined with chemotherapy or SBRT displayed promising anti-tumor activity in RM-NPC previously undergone PD-1 blockade, with a low toxicity profile. The increase of Treg in PBMCs is always associated with immune tolerance after PD-1 blockade and the decrease of Treg is correlated with benefit from Tislelizumab rechallenge.