Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis

Yuqin Song, Quanli Gao, Huilai Zhang, Lei Fan, Jianfeng Zhou, Dehui Zou, Wei Li, Haiyan Yang, Ting Liu, Quanshun Wang, Fangfang Lv, Haiyi Guo, Xia Zhao, Dan Wang, Pei Zhang, Yidi Wang, Lei Wang, Tengfei Liu, Yun Zhang, Zhirong Shen, Jane Huang, Jun Zhu, Yuqin Song, Quanli Gao, Huilai Zhang, Lei Fan, Jianfeng Zhou, Dehui Zou, Wei Li, Haiyan Yang, Ting Liu, Quanshun Wang, Fangfang Lv, Haiyi Guo, Xia Zhao, Dan Wang, Pei Zhang, Yidi Wang, Lei Wang, Tengfei Liu, Yun Zhang, Zhirong Shen, Jane Huang, Jun Zhu

Abstract

Purpose: Tislelizumab is an anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody specifically designed to minimize binding to Fcγ receptors (FcγR).

Patients and methods: Here, we present the extended 3-year follow-up of a phase II study of tislelizumab in 70 patients with relapsed/refractory classical Hodgkin lymphoma (cHL) who failed or were ineligible for autologous stem cell transplantation.

Results: With a median follow-up of 33.8 months, the overall response rate by the independent review committee was 87.1%, and the complete response (CR) rate was 67.1%. Responses were durable as shown by a median duration of response of 31.3 months, and median progression-free survival (PFS) of 31.5 months. The 3-year PFS and overall survival rates were 40.8% and 84.8%, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 97.1% of patients; the grade ≥3 TRAE rate was low (31.4%), and only 8.6% of patients experienced adverse events leading to treatment discontinuation. Correlative biomarker analysis showed that FcγRΙ-expressing macrophages had no observed impact on either the CR rate or PFS achieved with tislelizumab, which may be potentially related to its engineered Fc region.

Conclusions: With extended follow-up, tislelizumab yielded long-term benefits and demonstrated a favorable safety profile for patients with relapsed/refractory cHL. This trial was registered at clinicaltrials.gov as NCT03209973.

©2021 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
Forest plots of subgroup analyses of tislelizumab. A, Overall response rate. B, Complete response rate according to demographic and baseline disease characteristics. ASCT, autologous hematopoietic stem cell transplant; cHL, classical Hodgkin lymphoma; CI, confidence interval; CR, complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; ORR, overall response rate.
Figure 2.
Figure 2.
Progression-free survival by independent review committee per the Lugano classification. A, All treated patients. B, Patients achieving CR or PR + SD. C, Patients with/without prior ASCT. D, Patients with different number of lines of prior therapies (<3 vs. ≥3). ASCT, autologous hematopoietic stem cell transplant; CI, confidence interval; CR, complete response; NE, not estimable; PR, partial response; SD, stable disease.
Figure 3.
Figure 3.
Duration of response and overall survival. A, Duration of response in patients with an objective response by independent review committee per the Lugano classification. B, Overall survival for all treated patients. CI, confidence interval.
Figure 4.
Figure 4.
Associations of FcγRI+ macrophages in cHL tumor microenvironment with clinical outcomes of tislelizumab. A, Representative figure showing multiplex immunofluorescence staining (20× resolution) for CD8 T cells (CD8+ cells), total Fcγ receptor I (FcγRI+ cells), macrophages (CD68+ cells), FcγRI+ macrophages (FcγRI; CD68 double-positive cells), PDL1+, and CD30+ cells. B, CD8+ T cells, FcγRΙ+ macrophage infiltration, and their associations with complete response rates to tislelizumab. C, PFS by CD8+ T cells and FcγRΙ+ macrophages, divided by median cell percentage value of CD8 T cells and FcγRΙ+ macrophages separately. All mIHC images were acquired using Leica Aperio VERSA 8 auto-scanner. Note: (i) Make and model of microscope: LEICA DM6 B; (ii) Type, magnification, and numerical aperture of the objective lenses: ∞/0.17/OFM25/C, HC PL APO, 20×/0.80; (iii) Temperature: 20°C–30°C; (iv) Imaging medium: sCMOS: 23CAM014; (v) Fluorochromes: PerkinElmer Opal automation Multiplex IHC kit; (vi) Camera make and model: Andor Zyla 5.5; (vii) Acquisition software: Aperio VERSA. CR, complete response.
Figure 5.
Figure 5.
Heatmap of genes significantly associated with PFS by univariate Cox proportional hazards regression model. BOR, best overall response; CR, complete response; PFS, progression-free survival.

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