Blogs

Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma

RESEARCH

Summary:

The single-arm phase I/II study IMCgp100-102 (NCT02570308) examined the safety and efficacy of the bispecific antibody tebentafusp (gp100xCD3) in the treatment of patients with metastatic uveal melanoma (mUM) who have received at least one prior treatment. Previous results at median follow-up of 19.5 months reported an improved overall survival (OS). The data herein are a long-term follow-up analysis at 4 years, the longest follow-up of a T cell receptor bispecific antibody. The four-year OS rate was 14%. Safety data was consistent with previous reporting with no new concerns. Additionally, improved survival in patients with mUM was associated with lower ctDNA levels at baseline and a greater reduction in ctDNA by 9 weeks of treatment. These data suggest that ctDNA levels may be a good predictor of clinical benefit. In summary, while intensification or combination treatment may be needed, tebentafusp improves OS and is well tolerated long-term.

Understanding the dynamics of TKI-induced changes in the tumor immune microenvironment for improved therapeutic effect

RESEARCH

Summary:

Treatment with non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations have improved NSCLC outcomes. However, TKIs affect the tumor immune microenvironment (TME) which can lead to subsequent resistance to TKI therapy. This study examined the functional dynamics of the TME in both short- and long-term TKI treatment with the goal of improving strategies to treat NSCLC. Results showed that short-term TKI treatment boosts anti-tumor immunity by improving T cell-mediated tumor clearance and reducing M2 macrophage infiltration. Conversely, long-term TKI treatment leads to immunosuppression in the TME. Aspirin was identified as a potential adjunctive therapy to modulate the long-term effects by enhancing T cell-mediated tumor clearance. This study exemplifies the importance of the TME in resistance to TKI therapy and provides a potential easily-applied therapy, such as aspirin, to help overcome resistance in long-term treatment with TKIs.  

Distinct host preconditioning regimens differentially impact the antitumor potency of adoptively transferred Th17 cells

Summary:

Adoptive T-cell transfer (ACT) therapy is the method of infusing tumor-specific T cells into patients. Preconditioning regimens that cause lymphodepletion prior to adoptive cell therapy (ACT) are essential for transfer success. Previous research has shown two effective methods of lymphodepletion prior to transfer of anti-melanoma CD8⁺ T cells: total body irradiation (TBI) and cyclophosphamide (CTX). This study examined the efficacy of both methods prior to transfer of polarized T helper 17 (Th17) cells that recognized tyrosinase-related peptide (TRP)-1 melanoma antigen in melanoma-bearing mice. Results showed that TBI was more effective than CTX in allowing Th17 cells to engraft and facilitated a greater regression of melanoma. Additionally, following Th17 therapy, certain inflammatory cytokines were significantly elevated in the serum of the mice preconditioned with TBI versus CTX. These findings have shown that TBI may be a more effective preconditioning regimen for patients receiving Th17 ACT therapy and demonstrate the importance of research on preconditioning regimens across the ACT treatment landscape.

Autoantibody-positivity before and seroconversion during treatment with anti-PD-1 is associated with immune-related adverse events in patients with melanoma

Summary:

It is well established that treatment of cancer with immune checkpoint inhibitors (ICIs), such as anti-programmed cell death receptor-1 (PD-1), is often associated with immune-related adverse events (irAEs). Yet, there is currently no predictive biomarker to identify patients that may be at higher risk of developing irAEs when treated with ICIs. This retrospective study evaluated the association between the presence of baseline and/or seroconverted autoantibodies and the development of irAEs in patients with stage III or IV melanoma who received at least one dose of anti-PD-1. Baseline autoantibody positivity was found to be associated with the development of irAEs in all patients. There was also a strong association between the presence of anti-thyroid antibodies either at baseline or 3 months after treatment and thyroiditis, especially in female patients. Conversely, autoantibody positivity was not associated with disease recurrence or response. These data may be beneficial in guiding treatment options for patients exhibiting autoantibody positivity, considering that thyroid dysfunction may require lifelong replacement therapy.

The selections below represent some of the most popular content published in JITC over the past two years. Explore additional thematic content in JITC's Collections or access the rest of JITC's archives for a look at all the journal has to offer.

Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies
Patrick Schöffski, Daniel S W Tan, Miguel Martín, María Ochoa-de-Olza, John Sarantopoulos, Richard D Carvajal, Chrisann Kyi, Taito Esaki, Amy Prawira, Wallace Akerley, Filippo De Braud, Rina Hui, Tian Zhang, Ross A Soo, Michela Maur, Andrew Weickhardt, Jürgen Krauss, Barbara Deschler-Baier, Allen Lau, Tanay S Samant, Tyler Longmire, Niladri Roy Chowdhury, Catherine A Sabatos-Peyton, Nidhi Patel, Radha Ramesh, Tiancen Hu, Ana Carion, Daniel Gusenleitner, Padmaja Yerramilli-Rao, Vasileios Askoxylakis, Eunice L Kwak, David S Hong
Journal for ImmunoTherapy of Cancer 2022;10:e003776 (25 February, 2022)
RESEARCH

Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma
Jun Liu, Yang Yang, Zhichao Liu, Xiaolong Fu, Xiaoyue Cai, Hongxuan Li, Li Zhu, Yan Shen, Hong Zhang, Yifeng Sun, Hezhong Chen, Bentong Yu, Renquan Zhang, Jinchen Shao, Ming Zhang, Zhigang Li
Journal for ImmunoTherapy of Cancer 2022;10:e004291 (25 March 2022)
RESEARCH

The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL
Kai Rejeski, Ariel Perez, Gloria Iacoboni, Olaf Penack, Veit Bücklein, Liv Jentzsch, Dimitrios Mougiakakos, Grace Johnson, Brian Arciola, Cecilia Carpio, Viktoria Blumenberg, Eva Hoster, Lars Bullinger, Frederick L Locke, Michael von Bergwelt-Baildon, Andreas Mackensen, Wolfgang Bethge, Pere Barba, Michael D Jain, Marion Subklewe
Journal for ImmunoTherapy of Cancer 2022;10:e004475 (17 May 2022)
RESEARCH

A signature for pan-cancer prognosis based on neutrophil extracellular traps
Yi Zhang, Liping Guo, Qichen Dai, Bingqing Shang, Ting Xiao, Xuebing Di, Kaitai Zhang, Lin Feng, Jianzhong Shou, Yipeng Wang
Journal for ImmunoTherapy of Cancer 2022;10:e004210 (10 June 2022)
RESEARCH