(P 123) DEDIFFERENTIATED LIPOSARCOMAS TREATED WITH IMMUNE CHECKPOINT BLOCKADE: THE MD ANDERSON EXPERIENCE

Objective: Dedifferentiated liposarcoma (DDLPS) remains a difficult tumor to treat with few treatment options, and limited response to chemotherapy and targeted therapies. Previous trials in small cohorts of patients have reported objective response rates of 14-20% in DDLPS patients treated with immune-checkpoint blockade (ICB) [1, 2].The goals of this study were to determine response rate (RR) and survival with immune checkpoint blockade (ICB) treatment, and identify clinicopathologic factors associated with response and survival to ICB-based therapy in patients with DDLPS.

Methods: We retrospectively identified all pathologically confirmed patients with DDLPS treated with ICB at The University of Texas MD Anderson Cancer Center from 01/01/2018 to 01/01/2023. Baseline patient characteristics and RECIST radiographic response to ICB treatment, as per trial definition (if on trial) were collected. Clinical variables studied included age, sex, race, ethnicity, ECOG performance status, stage, location of primitive tumor, treatment history, clinical trial participation and treatment with combination ICB. Overall survival (OS) was defined as the time from diagnosis to death or last follow-up. Progression-free survival (PFS) was defined as the time from ICB start to progression, death, or last follow-up, whichever occurred first. OS and PFS were estimated by the Kaplan-Meier method [3]. Log-rank test was used to compare the survival distribution by baseline characteristics. The hazard ratio was estimated in Cox proportional hazard regression model. All analyses were performed in SAS 9.4 and R 4.2.3.

Results: Thirty-one patients received ICB therapy for DDLPS (Table 1) with a median follow-up from start of ICB of 51.7 months. The median age at receipt of ICB was 66 years (range 30 - 82). Thirteen patients (42%) received ICB as their first line of systemic therapy, while 18 patients (58%) received ICB after at least one line of systemic therapy. Twenty-eight patients (90%) received ICB as part of a clinical trial, with the majority administered for recurrent (n = 15; 48%) and metastatic (n = 11; 35%) disease. Out of all 31 patients, best response per treating physician or clinical trial definition, was progressive (PD), stable disease (SD), and partial response (PR) in 17 (55%), 12 (39%), and 2 (6%) patients (Figure 1), respectively. Median OS was 8.5 years (95% CI 4.3, 12.2); PFS was 3.4 months (95% CI 1.6, 4.2). Median OS since best response for patients with PD and SD was 12.1 months (95% CI 1.6, not reached) and 43.5 months (95% CI 11.6, not reached) respectively. Median duration of treatment by best response for PD was 1.8 months (range 0.9 – 4.7), SD 1.2 months (range 0 – 42.7), PR 2.6 months (range 0.9 – 4.2). Median time to best response for patients with PD, SD, and PR was 1.8 months (range 1.0, 4.7), 1.3 months (range 1.1, 2.7) and range of 0.4 to 2.1 months (n = 2) respectively. There were no clinical factors associated with PFS. Patients who received systemic therapy prior to ICB had inferior OS (HR=5.15 [95% CI 1.68-15.8, p = 0.004]) than those who received ICB as first systemic therapy (Figure 2). PFS was not associated with the number of prior lines of systemic therapy.

Conclusion: Although initial reports showed promising activity of ICB in DDLPS, our experience has been disappointing in this subtype of sarcoma. Other targeted strategies in combination with immune-based therapies may enhance this response rate and should be explored. Additional translational work may identify rationale for combinations.

References
1. Tawbi HA, Burgess M, Bolejack V et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 2017; 18: 1493-1501.
2. Chen JL, Mahoney MR, George S et al. A multicenter phase II study of nivolumab +/- ipilimumab for patients with metastatic sarcoma (Alliance A091401): Results of expansion cohorts. Journal of Clinical Oncology 2020; 38: 11511-11511.
3. Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. Journal of the American Statistical Association 1958; 53: 457-481.