1752P - A retrospective single-center study of outcomes to immune checkpoint blockade-based therapy in leiomyosarcoma

Background

Immune checkpoint inhibitors (ICI) have transformed the treatment landscape of several malignancies. However, their application in sarcomas have been limited to a few histotypes. Leiomyosarcoma (LMS), a mesenchymal tumor of smooth muscle origin, exhibits marked genomic heterogeneity and poor outcomes. Various studies have explored ICI in LMS with limited outcomes. In the largest series to date, we sought to comprehensively evaluate the role of ICI in LMS and identify genomic markers that might predict response.

Methods

We identified patients with LMS treated prospectively in the clinical trial setting with anti-PD1/PD-L1 therapy alone or in combination with other therapies and underwent MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing (NGS) testing. Patients with microsatellite instability (MSI) or tumor mutational burden (TMB) status determined were reviewed. Demographics, treatment history, and overall response rate (ORR) were extracted. Progression-free survival (PFS) was determined from Kaplan-Meier curves.

Results

A total of 60 patients were identified with 3 patients enrolled in more than 1 trial. The median (range) age was 59.1 (33-80) years, and 42 patients (70%) were female. 59.5% of female patients had uterine LMS subtype. All patients received anti-PD1/PD-L1 therapy alone or in combination with the following class of therapies: IDO1 inhibitor, anti-CTLA-4 Ab, PARP inhibitor, anti-CCR4, CSF-1R inhibitor, IL2 agonist, anti-AXL antibody-drug conjugate, VEGF inhibitor, oncolytic viral immunotherapy, or anti-PDGF-R. The median PFS was 8.43 weeks (95% CI: 0.36 - 0.60). ORR was 6.67% (4 patients). 2 of 4 patients with a partial response had alteration in BRCA1 or BRCA2 and received combination therapy with a PARP inhibitor. Median TMB (IQR) was 1.8 (0.9-3.5) mut/Mb. 2 patients had an MSI-high or TMB-H status (≥10 mut/Mb), but neither responded to treatment.

Conclusions

Despite numerous treatment strategies designed to overcome primary resistance to PD1/PD-L1 therapy, response to ICI remains limited in LMS. Neither MSI nor TMB status appear to be strong predictive markers for response to ICI in LMS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Institutes of Health.

Disclosure

C.M. Kelly: Financial Interests, Institutional, Advisory Board: ChemoCentryx, Exicure, Inc.; Non-Financial Interests, Advisory Board: Kartos Therapeutics, Inc. M. Gounder: Financial Interests, Advisory Role: Ayala Pharmaceuticals, Inc, Bayer, Boehringer Ingelheim, Guidepoint Global Advisors, Karyopharm, Med Learning Group, Rain Therapeutics Inc., Regeneron Pharmaceuticals, Inc., SpringWorks Therapeutics, Syneos Health, UptoDate. R.G. Maki: Financial Interests, Personal, Other, DSMB participation: Deciphera; Financial Interests, Personal, Other, Consultant to serve as Medical Monitor: Peel Therapeutics; Financial Interests, Personal, Invited Speaker, Sarcoma content for web site: Physician's Education Resource; Financial Interests, Personal, Writing Engagement, Sarcoma content editor: UptoDate; Financial Interests, Personal, Advisory Board, Advisory board: GSK; Financial Interests, Personal, Advisory Board: Medtronic; Financial Interests, Personal, Other, Associate Editor, JCO: American Society of Clinical Oncology; Financial Interests, Personal and Institutional, Coordinating PI, Clinical trial support and steering committee - brigimadlin studies: Boeringher Ingelheim; Financial Interests, Personal and Institutional, Coordinating PI, Investigator initiated trial with pembrolizumab: GSK. P. Chi: Financial Interests, Personal, Other, Advisor and Consultant: Ningbo NewBay Medical Technology; Financial Interests, Institutional, Funding, Clinical trial funding: Ningbo NewBay Medical Technology; Financial Interests, Personal and Institutional, Steering Committee Member, Clinical Trial: Ningbo NewBay Medical Technology, Deciphera; Financial Interests, Institutional, Funding, clinical trial: Deciphera; Financial Interests, Institutional, Funding, Trial: Pfizer. W.D. Tap: Financial Interests, Advisory Role: AmMax Bio, Inc., Amgen, BioAtla, Inc., Boehringer Ingelheim, Cogent Biosciences, Inc., Connecting Humans in Health, LLC, Daiichi Sankyo, Deciphera, Inhibrx, Inc., Osteosarcoma Institute (OSI), PER Events, LLC, PeerView Institute for Medical Education (PVI), Projects in Knowledge, Servier; Financial Interests, Ownership Interest: Atropos Therapeutics, Inc., Certis Oncology Solutions. S.P. D'Angelo: Financial Interests, Advisory Role: Aadi Bioscience, Inc., Adaptimmune, GI Innovation Inc., GSK, Pfizer, Inc., Servier. S. Movva: Financial Interests, Institutional, Coordinating PI: Tracon, Pfizer, Merck, BMS, Clovis, Ascentage; Financial Interests, Institutional, Local PI: PTC therapeutics, Hutchinson Medipharma. All other authors have declared no conflicts of interest.