In recent years, our understanding of the epigenetic mechanisms involved in tumor pathology has improved greatly. DNA and histone modifications, such as methylation, demethylation, acetylation, and deacetylation, can lead to the up-regulation of oncogenic genes, as well as the suppression of tumor suppressor genes. Gene expression can also be modified on a post-transcriptional level by microRNAs that contribute to carcinogenesis. The role of these modifications has been already described in many tumors, e.g., colorectal, breast, and prostate cancers. These mechanisms have also begun to be investigated in less common tumors, such as sarcomas. Chondrosarcoma (CS) is a rare type of tumor that belongs to sarcomas and is the second most common malignant bone tumor after osteosarcoma. Due to unknown pathogenesis and resistance to chemo- and radiotherapies of these tumors, there is a need to develop new potential therapies against CS. In this review, we summarize current knowledge on the influence of epigenetic alterations in the pathogenesis of CS by discussing potential candidates for future therapies. We also emphasize ongoing clinical trials that use drugs targeting epigenetic modifications in CS treatment.

e21552 Background: Nivolumab plus ipilimumab (NIVO+IPI), a first-in-class combination immunotherapy, has dramatically changed the treatment paradigm for melanoma in recent years. The aim of this study was to analyze treatment patterns, treatment response, survival, safety, and healthcare resource utilization with this first-line combination therapy in patients (pts) with advanced melanoma under real-world conditions. Methods: This retrospective analysis included pts with stage 3 unresectable and stage 4 melanoma treated 01/2021-06/2022 with NIVO+IPI at 6 centers in Poland according to uniform criteria. Pts received up to 4 cycles of IPI 3 mg/kg + NIVO 1 mg/kg Q3W followed by maintenance NIVO (240 mg Q2W or 480 mg Q4W) until disease progression, unacceptable toxicity or at the request of the patient or physician. Kaplan-Meier estimator and Log-rank test were used in survival analysis. Results: A total of 291 adults were identified. The median age was 53 years, 42.5% of pts were female, 47% were BRAF-mutated, and 24% of pts received prior adjuvant treatment. At baseline, 19.5% of pts had stage III disease, 14.1% stage M1a, 13.7% stage M1b, 30.1% stage M1c and 23% had M1d disease. Median follow-up time was 11.9 months. The median number of cycles of NIVO+IPI administered was 3, with 47.9% of pts completing 4 cycles. Maintenance NIVO was continued in 52.7% pts who discontinued the combination therapy due to toxicity. Median progression-free survival (mPFS) was 9.8 months (95% CI 6.9–13.4). The longest mPFS was observed in pts with stage M1a (15 months; 95%Cl 3.1–NA) and the shortest in stage M1d pts (5 months; 95%CI 2.8–NA). We observed a statistically significant longer mPFS in pts who continued NIVO monotherapy after discontinuation of combination therapy due to toxicity (13 months, 95% Cl 10.4–NA) compared to those who discontinued immunotherapy (7.1 months, 95% Cl 3.4 –12; p < 0.0001). Median overall survival (OS) was not achieved, with an OS rate of 70% at 12 months (95%Cl 64–76). The objective response rate (ORR) was 39%, with 7.8% of pts achieving a complete response. For pts who received prior adjuvant therapy, the ORR was 24.2%. Treatment-related adverse events (TRAEs) of any grade were observed in 97% of pts and grade 3/4 TRAEs occurred in 29.6% of pts. The most common TRAEs were liver toxicity, colitis, hyperthyroidism, hypothyroidism, and hypopituitarism; the treatment-related hospitalization rate was 23.8% and the median length of hospital stay was 9 days. Conclusions: This real-world study confirms the high efficacy of NIVO+IPI in real-world settings with grade 3/4 toxicity lower than observed in clinical trials. Maintenance of NIVO despite early toxicity during combination treatment appears to have a beneficial effect on patient survival. Therefore, it is extremely important to carefully monitor pts for toxicity, as early intervention helps to avoid severe toxicity and premature discontinuation of treatment.