From December 6 to 9, 2025, the 67th Annual Meeting of the American Society of Hematology (ASH) was held in Orlando, bringing together the latest global research and clinical advances in hematology. This report highlights three studies from Professor Chengcheng Fu’s team at the First Affiliated Hospital of Soochow University, focusing on novel therapies for relapsed or refractory multiple myeloma (MM), MRD-driven treatment strategies for newly diagnosed high-risk MM, and the prognostic impact of sustained minimal residual disease (MRD) negativity. Together, these studies outline emerging treatment directions and provide important guidance for clinical decision-making in multiple myeloma.
01 ASH Poster #2278
Title: GT919, a Novel IKZF3/1 Molecular Glue Degrader: Phase 1 Safety and Preliminary Efficacy in Relapsed or Refractory Multiple Myeloma Authors: Chengcheng Fu, Xuhong Fu, Bing Chen, Qingsong Yin, Songfu Jiang, Jingjing Shang, Chaoyang Guan, Song Jin, Yingying Zhai, Xiuyi Song, Xiaobao Yang, Depu Wu Affiliations: Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Biaoxin Biopharmaceutical Technology (Shanghai) Co., Ltd., Shanghai, China; Department of Hematology, Nanjing Drum Tower Hospital, Nanjing, China; Henan Cancer Hospital, Zhengzhou, China; Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Background The pathogenesis of multiple myeloma is critically regulated by transcription factors IKZF3 and IKZF1, which are essential for plasma cell differentiation. Immunomodulatory drugs (IMiDs) exert anti-myeloma effects by inducing CRBN E3 ligase–mediated ubiquitination and degradation of IKZF3/1. GT919 is a novel, oral, highly selective molecular glue degrader that induces efficient CRBN-dependent degradation of IKZF3 and IKZF1. Preclinical studies demonstrated potent degradation at low nanomolar concentrations and activity in lenalidomide- or pomalidomide-resistant MM cell lines and xenograft models. At ASH 2025, results from this first-in-human study (CTR20231255) were presented, evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GT919 in relapsed or refractory MM.
Methods This was an open-label, multicenter phase 1 study consisting of a standard 3+3 dose-escalation phase followed by dose expansion. GT919 was administered in 28-day cycles (21 days on, 7 days off) in combination with dexamethasone. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Patients in part A were refractory to at least one proteasome inhibitor and one IMiD, while those in part B were refractory to proteasome inhibitors, IMiDs, and anti-CD38 monoclonal antibodies.
Results As of July 2025, 29 Chinese patients with relapsed or refractory MM were enrolled, with a median age of 69 years and a median of three prior lines of therapy. All patients were refractory to proteasome inhibitors and IMiDs, and 68% were triple-refractory. No dose-limiting toxicities were observed. Treatment-emergent adverse events occurred in all patients, with grade ≥3 treatment-related adverse events in 46%, mainly neutropenia, pneumonia, upper respiratory tract infection, and thrombocytopenia. Hematologic toxicities were transient and largely limited to the first two cycles. No treatment discontinuations, dose reductions, or deaths related to GT919 were reported.
Pharmacodynamic analyses demonstrated effective IKZF3 degradation and T-cell activation at doses ≥2 mg, with concurrent IKZF1 degradation observed at 4 mg. Among patients treated with ≥2 mg GT919 plus dexamethasone, the overall response rate was 36%, with a clinical benefit rate of 45%. At a median follow-up of 5.2 months, median progression-free survival and duration of response had not been reached, with the longest ongoing PFS exceeding 22 months.
Conclusion GT919 combined with dexamethasone demonstrated a manageable safety profile and promising preliminary efficacy in relapsed or refractory MM. Based on safety review committee recommendations, the recommended phase 2 dose was determined to be 4 mg, and a phase 2 combination study is planned.
02 ASH Poster #5782
Title: MRD-Guided Treatment in Newly Diagnosed High-Risk Multiple Myeloma Using Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone
Background High-risk multiple myeloma is characterized by aggressive biology and poor survival outcomes under standard therapies. With advances in MRD detection, MRD negativity has emerged as both a marker of deep response and a strong prognostic indicator, providing a rationale for MRD-driven treatment strategies. The DKRD regimen has shown superior efficacy in high-risk MM in international studies and is recommended by guidelines. This study aimed to evaluate the efficacy and safety of DKRD in newly diagnosed high-risk MM in a real-world Chinese cohort.
Methods This was a prospective, single-center, single-arm study enrolling 58 newly diagnosed high-risk MM patients. Patients received one cycle of VRD followed by three cycles of DKRD. Transplant-eligible patients underwent stem cell collection and autologous transplantation, followed by consolidation and maintenance therapy. The primary endpoint was MRD negativity after consolidation, assessed by NGF and NGS.
Results Patients had a high tumor burden and complex cytogenetic abnormalities. The overall response rate after induction was 92.8%, with deep responses continuing after transplantation and consolidation. NGF-MRD negativity rates reached over 80% after induction and exceeded 90% after transplantation. The regimen was generally well tolerated, with manageable hematologic and non-hematologic toxicities, and did not compromise stem cell collection.
Conclusion Despite high-risk features, the DKRD regimen achieved high response and MRD negativity rates with an acceptable safety profile, translating into meaningful survival benefits for newly diagnosed high-risk MM patients.
03 ASH Poster #5796
Title: Sustained MRD Negativity Assessed by NGS and NGF Overcomes High-Risk Cytogenetics and Predicts Survival in Transplant-Eligible Multiple Myeloma
Background Whether sustained MRD negativity at high sensitivity can mitigate the adverse prognosis associated with high-risk cytogenetics remains unclear. This real-world study evaluated the prognostic significance of sustained MRD negativity assessed by both NGS and NGF.
Methods A total of 242 newly diagnosed MM patients undergoing autologous stem cell transplantation were monitored longitudinally for MRD using NGS and NGF. Sustained MRD negativity was defined as concordant negative results by both methods on at least two assessments separated by at least one year.
Results MRD negativity was achieved by 59.6% of patients and was associated with significantly improved progression-free survival. Sustained MRD negativity emerged as the strongest independent predictor of PFS and effectively neutralized the adverse impact of high-risk cytogenetics, including double-hit disease. Loss of sustained MRD negativity predicted accelerated disease progression.
Conclusion Sustained MRD negativity confirmed by multimodal high-sensitivity methods represents a functional cure threshold in multiple myeloma, transcending baseline risk and supporting its adoption as a key endpoint in clinical trials and practice.
Expert Profile
Professor Chengcheng Fu The First Affiliated Hospital of Soochow University Deputy Director, Department of Hematology; Chief Physician; Associate Professor; Doctoral Supervisor
Professor Fu is actively involved in national and international myeloma research networks and has led multiple funded projects at provincial and national levels. Her work has significantly contributed to advancing precision treatment and MRD-guided strategies in multiple myeloma.
