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Dana-Farber to present more than 30 research studies at 2021 ASH Annual Meeting

Dana-Farber study selected for inclusion in the official ASH press program 

Dana-Farber Cancer Institute researchers will present more than 30 research studies at the virtual 63rd American Society of Hematology (ASH) Annual Meeting on December 11-14, including one study that was selected to be presented in the official press program. Dana-Farber has one of the largest and most respected treatment centers for patients with disorders of the blood and bone marrow.  

ASH is the world's most comprehensive hematology event, attracting more than 20,000 hematology professionals from around the world. Scientific updates to be presented at the 2021 ASH Annual Meeting reveal potentially practice changing findings related to understanding and treating multiple myeloma, lymphoma, leukemia, and other blood cancers.  Notable oral presentations by Dana-Farber researchers include: 

Title: High prevalence of monoclonal gammopathy in a population at risk: The first results of the Promise Study* 

Abstract: 152  

Senior Author: Irene Ghobrial, MD 

Presenter: Habib El-Khoury, MD  

Press Program Time: Saturday, Dec. 11, 10:30-11:30 a.m. EST  

Session Time: Saturday, Dec. 11, 12:15 p.m.  

Multiple myeloma evolves from monoclonal gammopathy of undetermined significance (MGUS), a clinically detectable but asymptomatic premalignant phase seen in ~3% of the general population 50 years of age or older. The prevalence of MGUS has not been described in a population at high risk of developing myeloma, specifically African American individuals or first-degree relatives of patients with hematologic malignancies. In 2019, Dana-Farber investigators launched the PROMISE study, the first nationwide U.S. screening study for individuals at high risk of myeloma to help better identify what population would benefit most from screening and early intervention for precursor stages. Researchers aim to assess the prevalence of MGUS in a population at high risk of myeloma and characterize clinical variables of individuals who screen positive. Dana-Farber researchers will report interim screening data on the first 2,960 participants. 

Title: Single-Cell RNA-sequencing identifies immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma 

Abstract: 330  

Author: Romanos Sklavenitis-Pistofidis, MD 

Session Time: Saturday, Dec. 11, 5:15 p.m.  

Patients with smoldering multiple myeloma (SMM) are typically observed until progression to overt multiple myeloma, but early treatment of high-risk patients may improve outcomes. Clinical and genomic biomarkers can help to identify SMM patients at high risk of progression, but whether parallel profiling of the tumor immune microenvironment can further improve models remains to be determined. 

Title: Inadequate Sars-Cov-2 vaccine effectiveness in patients with multiple myeloma: A large nationwide Veterans Affairs study 

Abstract: 400  

Author: Nikhil Munshi, MD 

Session Time: Sunday, Dec. 12, 10:15 a.m. 

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is particularly serious in patients with multiple myeloma, with estimated mortality of over 30% in several studies. In the general population, SARS-CoV-2 vaccination has been demonstrated to be an effective approach to preventing infection. However, patients with myeloma were not included in vaccination trials. Recent studies suggest that patients with compromised immune systems exhibit reduced antibody response to SARS-CoV-2 vaccination, and myeloma patients are often immunocompromised both due to myeloma itself and their treatment. This retrospective cohort study in the national Veterans Affairs healthcare system evaluates the real-world effectiveness of SARS-CoV-2 vaccination to prevent COVID-19 infection in myeloma patients during the 140-day period following initial vaccine availability. 

Title: Defining genomic probability of progression to identify low-risk smoldering multiple myeloma 

Abstract: 545  

Author: Anil Aktas-Samur, PhD 

Session Time: Sunday, Dec. 12, 5:30 p.m.  

On an average, 1% of monoclonal gammopathy of undermined significance (MGUS) and 10% of smoldering multiple myeloma (SMM) progress to symptomatic myeloma every year within the first five years of diagnosis. The probability of progression significantly decreases for SMM patients after the first five years. However, a distinct subset of SMM patients progress within two years and are re-classified as high-risk patients based on risk markers such as 20/2/20 or certain genomic features. Although recent studies have evaluated the high-risk genomic features for SMM but genomic background of SMM patients who do not progress to myeloma after long-term follow-up (>= 5 years) has not been described. 

Title: Identification of a novel epigenetic mechanism of MYC Deregulation in smoldering and newly diagnosed multiple myeloma patients  

Abstract: 504 

Author: Mahshid Rahmat, PhD 

Session Time: Sunday, Dec. 12, 5:45 p.m.  

Enhanced expression of the MYC oncogene is associated with the initiation and maintenance of many human cancers, including multiple myeloma. Myeloma is a malignancy of clonal plasma cells, in which MYC deregulation is a key event in the progression from the precursor stages of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to symptomatic myeloma. Translocation and amplification of the 8q24.21 MYC locus are known mediators of MYC deregulation at premalignant stages for some patients. However, DNA and RNA sequencing of patients show that cases with an intact MYC locus also exhibit MYC deregulation, indicating that additional mechanisms are involved in the deregulation of MYC in myeloma. In this presentation, Dana-Farber researchers describe a new epigenetic mechanism of transcriptional deregulation of MYC in malignant plasma cells. Results show that activation of a novel non-coding regulatory region through the binding of myeloma-specific transcription factors (TFs) is associated with MYC dysregulation in myeloma. 

Title: Longer term follow-up of a multicenter, phase 2 study of Ibrutinib plus Fludarabine, Cyclophosphamide, Rituximab (iFCR) as initial therapy for younger patients with chronic lymphocytic leukemia 

Abstract: 640 

Author: Matthew Davids, MD, MMSc 

Session Time: Monday, Dec. 13, 11:15 a.m. 

Fludarabine, Cyclophosphamide, Rituximab (FCR) regimen remains the only therapy other than allogeneic transplant proven to provide a significant chance of functional cure with very long-term follow-up for young, fit patients with mutated IGHV chronic lymphocytic leukemia (CLL). Given the excellent efficacy and tolerability of ibrutinib in a broad population of young, fit CLL patients, investigators designed the frontline iFCR study to determine whether time-limited novel agent plus chemoimmunotherapy could provide durable remission for CLL patients irrespective of IGHV status. Dana-Farber researchers previously reported that with a median follow-up of 16.5 months, the rate of complete response with bone marrow undetectable minimal residual disease (BM-uMRD) 2 months post-FCR (primary endpoint) was 33%, and that 84% of patients achieved BM-uMRD as best response. At ASH, Dana-Farber researchers report updated data with longer follow-up, with all patients having had the opportunity to complete two years of ibrutinib maintenance following iFCR. 

Title: Genomic profiling of smoldering multiple myeloma classifies molecular groups with distinct pathogenic phenotypes and clinical outcomes  

Abstract: 723  

Author: Irene Ghobrial, MD 

Session Time: Monday, Dec. 13, 3:15 p.m. 

Multiple myeloma is an incurable plasma cell malignancy commonly preceded by the asymptomatic stage smoldering multiple myeloma (SMM). Myeloma is characterized with significant genomic heterogeneity of chromosomal gains and losses (CNVs), translocations, and point mutations (SNVs); alterations that are also observed in SMM patients. However, current SMM risk models rely solely on clinical markers and do not accurately capture progression risk. While incorporating some genomic biomarkers improves prediction, using all myeloma genomic features to comprehensively stratify patients may increase risk stratification precision in SMM. 

In addition, two Dana-Farber faculty members will be honored at the meeting. Margaret Shipp, MD, will receive the Ernest Beutler Lecture and Prize. The award recognizes the work of Dr. Shipp to understand the genomics of Hodgkin lymphoma and its effects on the tumor environment. Donna Neuberg, ScD, will receive the 2021 Exemplary Service Award for her years of service and dedication to ASH and to hematology. Dr. Matthew Davids will give a lecture at the ASH Presidential Symposium, discussing current therapeutic strategies to inhibit or reactivate mutant p53 and its pathway in both acute and chronic hematologic malignancies now that a number of active agents are available.  

Complete details on Dana-Farber’s activities at ASH are available online at www.dana-farber.org/ash 

For all ASH-related media inquiries, call or email Claire Monaghan, 240-678-6494, claire_monaghan@dfci.harvard.edu.  

*Denotes study selected for the 2021 ASH Annual Meeting press program  

Posted on December 07, 2021

  • Research
  • Nikhil C. Munshi, MD
  • Irene Ghobrial, MD
  • Matthew S. Davids, MD, MMSc
  • Multiple Myeloma
  • Chronic Lymphocytic - CLL
  • Blood Cancer

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