Editorial Note: The 2024 American Society of Hematology (ASH) Annual Meeting, held from December 7 to 10 in San Diego, continues to be a global focal point for clinicians and researchers in hematology. As one of the most prestigious international conferences in the field, it has captured widespread attention both globally and within China. To provide timely updates on the most significant developments at the conference, Oncology Frontier - Hematology Frontier launched the "ASH Daily News Highlights" series. Dr. Jun Zhu from Peking University Cancer Hospital serves as the series host, connecting daily with onsite experts to bring firsthand updates. On the third day of the conference, we were honored to hear from Dr. Wenming Chen of Beijing Chaoyang Hospital, who shared insights into key studies in the field of myeloma.

Dr. Jun Zhu:Professor Chen, thank you for joining us. As the third day of the ASH conference winds down, could you share the most notable research findings in the field of multiple myeloma?

Dr. Wenming Chen:Thank you, Professor Zhu. Reporting live from ASH, here are some of the most impactful basic and clinical research findings in the field of myeloma that caught my attention today (December 9).

Gene Transcriptomics Research: Paving the Way for New Myeloma Targets

A gene transcriptomics study from Maryland, USA, stood out as particularly noteworthy. Multiple myeloma (MM) develops from oncogenic transcription programs built on transcription networks found in normal plasma cells. The transcription factor IRF4 establishes plasma cell identity, but in myeloma cells, additional transcription factors—most prominently MYC—are recruited to amplify transcription, driving the growth and survival of malignant plasma cells.

This study identified 645 and 576 genes essential for IRF4 and MYC expression, respectively. Among these, the researchers highlighted the SWI/SNF chromatin remodeling gene family, common mediator complex components, and cyclin-dependent kinase 8 (CDK8), suggesting that the CDK8 subcomplex could be a potential target to disrupt the IRF4-MYC autoregulatory loop in multiple myeloma.

Using computational modeling, the researchers screened over 2,000 compounds targeting this pathway and identified three with high clinical potential: MEK inhibitors, mTOR inhibitors, and CDK8 inhibitors. The study showed that MED12 and the CDK8 subcomplex play a critical role in oncogenic transcription in MM. Selective small-molecule inhibitors targeting this subcomplex, combined with established therapies, may offer a novel precision medicine strategy for MM.

This research not only brings new hope to myeloma treatment but also offers valuable insights for Chinese researchers, as there remains a gap in transcriptomics and computational modeling between China and other leading nations in this field.

IMROZ Phase III Study: Latest Results for Newly Diagnosed MM

The IMROZ study is a global Phase III clinical trial comparing Isa-VRd (isatuximab, bortezomib, lenalidomide, and dexamethasone) with VRd (bortezomib, lenalidomide, and dexamethasone) in newly diagnosed MM patients ineligible for transplant. Previous presentations of this study have reported on various outcomes. At this conference, the focus was on the dynamics of minimal residual disease (MRD) over time.

Results showed that the Isa-VRd regimen achieved a higher proportion of MRD negativity compared to the VRd group, both at the end of maintenance and throughout the maintenance phase. The depth of MRD-negative remission improved over time, with higher proportions of sustained MRD negativity at sensitivity thresholds of 10−510^{-5}10−5 and 10−610^{-6}10−6. More patients maintained MRD negativity during the maintenance phase with the Isa-VRd regimen.

In summary, Isa-VRd outperformed VRd in MRD negativity across all disease stages and severities, translating into longer progression-free survival (PFS). We eagerly anticipate additional data from this trial during the conference.

DREAMM-7 Phase III Study: New Data on Relapsed/Refractory MM

The DREAMM-7 trial is a global randomized, open-label Phase III study evaluating two triplet regimens for relapsed/refractory MM patients who had received at least one prior line of therapy:

• BVd: Belantamab mafodotin (an ADC drug), bortezomib, and dexamethasone
• DVd: Daratumumab, bortezomib, and dexamethasone

Previous reports indicated significantly longer progression-free survival (PFS) with the BVd regimen compared to DVd. This conference presented updated results focusing on overall survival (OS).

The BVd regimen demonstrated a significant OS benefit over DVd. Long-term follow-up results reinforced the superior efficacy of BVd in treating relapsed/refractory MM, positioning it as a potentially preferred option for earlier lines of treatment.

Dr. Jun Zhu:

Thank you, Professor Chen, for bringing us these compelling updates from ASH. From breakthroughs in basic research to clinical advancements, your insights on these key findings in the field of myeloma highlight the potential for significant changes in clinical practice. These studies not only provide important directions for future research but also offer hope for improved patient outcomes. Thank you again for your valuable contributions.

Dr. Wenming Chen is a Chief Physician and Doctoral Supervisor at Beijing Chaoyang Hospital’s Department of Hematology. He serves as the leader of Beijing’s multi-disciplinary talent team for multiple myeloma, a member of the International Myeloma Working Group (IMWG), and a council member of the Asian Myeloma Network (AMN), where he received the IMF-AMN Outstanding Service Award.

Professor Chen is actively involved in numerous academic and clinical organizations, including the Chinese Medical Education Association and the Chinese Society of Hematology. His extensive research and leadership roles span areas such as hematology, bone marrow transplantation, and precision medicine in multiple myeloma.

Chair, Department of Lymphoma, Peking University Cancer Hospital

Renowned expert in lymphoma, serving in various leadership roles within national and international oncology associations.