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4600 Anti-PD-1 Antibody (Sintilimab) Plus Decitabine As First Line Treatment for Patients with Higher-Risk Myelodysplastic Syndrome (MDS): Primary Results from a Single-Arm,Open-Label,Phase II Study

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Monday, December 11, 2023, 6:00 PM-8:00 PM

Jing Wang, MD1*, Siqi Li, MS2*, Hao Jiang3*, Ying-Jun Chang4*, Xiao-su Zhao5*, Jinsong JIA, MD, PhD3*, Xiaolu Zhu, MD5*, Lizhong Gong1*, Xiaohong Liu6*, Wen-Jing Yu7* and Xiaojun Huang8*

1Peking University People’s Hospital,Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China
2Peking University People’s Hospital, Beijing, AL, CHN
3Peking University People’s Hospital, Beijing, CHN
4Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
5Peking University People’s Hospital, Beijing, China
6Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China
7Peking University People's Hospital, Beijing, CHN
8Peking University People's Hospital,Institute of Hematology, Beijing, Wisconsin, CHN

Background: Hypomethylating agents (HMAs) are the preferred treatment for untreated patients with higher-risk Myelodysplastic Syndrome (MDS). However, the survival rate of patients after HMA treatment remains poor. Studies have shown that HMAs upregulate the expression of PD-1/PD-L1 in MDS patients, making the combination of HMAs with PD-1 antibodies a compelling approach for MDS treatment. Consequently, we conducted this single-arm, open-label clinical trial (ChiCTR2100044393) to assess the safety and efficacy of sintilimab in combination with decitabine for patients with higher-risk MDS.

Methods: Adult patients with higher-risk MDS, according to the IPSS-R, were eligible for enrollment in this study. The treatment regimen consisted of daily intravenous administration of decitabine at a dose of 20mg/m2 for 5 consecutive days, along with intravenous administration of sintilimab at 200mg on the first and 22nd day of a 42-day treatment cycle. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of consent, or other protocol-defined reasons, with a maximum of 8 cycles allowed. The primary endpoint of this study was the overall response rate (ORR). To determine the sample size, we utilized Simon's optimal two-stage design. Secondary endpoints included the assessment of safety and various survival outcomes. Additionally, we investigated the relationship between the expression levels of immune checkpoints and the efficacy of the combination therapy and other potential biomarkers through genomic profiling.

Results: As of the data cut-off on June 16, 2023, 53 patients were enrolled, with a median follow-up time of 14 months, and 52 patients were eligible for response evaluation. The median age of patients was 65 years (range 19-83), other characteristics were summarized in Table 1.The ORR was 76.9%, and 15 patients achieved complete response (CR), 13 marrow complete response(mCR),7 mCR+ hematologic improvement(HI), and 5 HI. Among the 40 responders, six patients (4 with CR and 2 with mCR) underwent allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) has not reached, and the median event-free survival (EFS) was 16 months. The 24-month OS and EFS rates were 54.8% (95%CI: 39.5-76.2) and 46.2% (95%CI: 31.2-68.3), respectively. The most common grade 3 or higher treatment-emergent adverse events (TEAEs) reported in 10% or more of the patients were febrile neutropenia (67.9%) and pulmonary infection (20.8%). A total of 17 patients (32.1%) experienced immune-related adverse events (irAEs), with the most common irAEs being rash (17.0%), thyroid dysfunction (9.4%), and pneumonia (7.5%), all resolved after glucocorticoid treatment. Regarding genetic mutations, the most frequently mutated genes were ASXL1 (34.0%), RUNX1 (30.2%), TET2 (17.0%), and U2AF1 (17.0%).

Conclusion: To the best of our knowledge, this is the first study evaluating the efficacy and safety of the combination therapy with sintilimab and decitabine in previously untreated patients with higher-risk MDS. This regimen showed an encouraging anti-tumor activity with a manageable safety profile.

Disclosures: No relevant conflicts of interest to declare.

OffLabel Disclosure: Sintilimab is a fully human IgG4 monoclonal antibody, which specifically binds to PD-1 expressed on the surface of T cells to block the interaction between PD-L1 and PD-1, thereby reinvigorating exhausted T cell to gain effector function to kill tumor cells.In December 2018, TYVYT® (sintilimab injection) was first approved by the China NMPA for the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy.

*signifies non-member of ASH