Working Group Chairs

With the advent of new scientific advances—such as such as genomics, proteomics, and the development of new technologies—scientists are now equipped with new tools to advance research efforts that did not exist just a few years ago. Recognizing the tremendous opportunities these scientific and technological advances present, the MMRF sought to evolve its Scientific Agenda to apply these exciting advances to the field of myeloma. This would ensure that we maximize each dollar raised by funding innovative research efforts that offer the greatest potential to advance myeloma research and drug discovery. In developing this Agenda, the MMRF brought together the world's most prominent and renowned clinicians, researchers, and thought leaders from a broad spectrum of disciplines, including: Julian Adams, Infinity Pharmaceuticals; Brian Druker, Oregon Health & Science University; Todd Golub, Broad Institute; David Parkinson, Amgen Inc.; Louis Staudt, National Cancer Institute.

Together, we undertook an ambitious four-phased process to evaluate the state of myeloma research, and to prioritize future research directions with the greatest potential.

• Phase I: Interviews with the Experts
• First, we conducted extensive interviews more than 20 experts from diverse scientific and medical disciplines to identify and prioritize key research areas, and to determine how recent advances in science and cutting-edge technologies could be applied to myeloma.
  
  
• Phase II: Spending Analysis
• Next, we analyzed spending patterns at the National Cancer Institute (NCI) and the MMRF to better understand where funds have been used and are currently being used.
  
  
• Phase III: Gap Analysis
• We then overlaid our spending analysis with priority areas identified in Phase I to develop a comprehensive gap analysis.
  
  
• Phase IV: Scientific Research Roundtable
• Finally, we convened leaders from a broad cross-section of the scientific and medical community at a veritable "meeting of the minds" to develop a detailed plan to advance science quickly and effectively.

This process was unique, not only in the caliber of the individuals who participated, but in its rigorous methodology. As such, it is widely regarded by the scientific community as inventive and pioneering, and will likely serve as a useful model for other research organizations seeking to advance their research efforts. From these proceedings, three key research areas that are critical in advancing myeloma research and drug development were identified. Working groups were established in each focus area to identify key research objectives, as well as to create a focused research portfolio to meet these objectives.

• Genomics and Proteomics
• Working Group Chairs: Brian Druker, MD, Oregon Health and Science University Patrick Klein, PhD, Broad Institute of Harvard and MIT
• Research efforts focus on developing an improved understanding of the biology of multiple myeloma and identifying key targets that cause the disease to develop and progress. A greater understanding of the genetic complexities of myeloma will lay the groundwork for the development of individualized therapies.
  
  
• Target and Compound Validation and Prioritization
• Working Group Chairs: Kenneth Anderson, MD, Dana-Farber Cancer Institute Ellen Feigal, MD, Translational Genomics Research Institute
• Research efforts focus on the robust validation of existing compounds, as well as the validation of new, druggable targets for myeloma. These are important first steps in developing effective new and combination treatments for the disease.
  
  
• Clinical Trials and Correlative Science
• Working Group Chairs: Alison Hannah, MD, Consultant Sundar Jagannath, MD, Saint Vincent's Comprehensive Cancer Center
• Research efforts focus on improving the design and implementation of high-quality clinical trials to bring new and combination therapies from the laboratory to the clinic as quickly as possible. Additionally, these efforts focus on initiating strong correlative analyses to determine why a particular drug is effective in some patients but not others—an important first step in developing individualized treatments for myeloma.

Designed to have both immediate and long-lasting impact, these programs aim not only to drive new therapies to patients who need them today, but to significantly improve our understanding of the disease.

Genomics and Proteomics

• A genome mapping program to accelerate the pace of myeloma discovery by laying a foundation of molecular understanding of the disease. This novel effort includes seven related discovery efforts spanning the spectrum of genomic research, including gene expression profiling to advance the molecular subclassification of cancers and investigation into potential molecular targets, and exon resequencing to identify genes thought to play a role in the onset of progression of myeloma or cancer in general.
  
  
• Expansion of the Multiple Myeloma Research Consortium's (MMRC) Tissue Bank with samples from additional research sites, creating the critical mass of high-quality tissue samples needed to validate promising new compounds and druggable targets.
  
  
• A Focus on proteomics to identify potential research opportunities to apply these cutting-edge technologies to myeloma.

Compound and Target Validation and Prioritization

• A drug screening project to validate existing FDA-approved drugs and other available compounds against known myeloma targets as a first step in developing these compounds into myeloma treatments.
  
  
• Development of a web-based "myeloma portal." This comprehensive, searchable database will allow us to track every compound and target undergoing validation, every ongoing and anticipated clinical trial, and every company pursuing myeloma. This will not only enable us to pinpoint where compounds are in the drug development process, but will reduce the duplication of efforts.
  
  
• A Research Roundtable to develop an optimal compound validation algorithm to determine how to best validate new and existing compounds. The Research Roundtable to outline this algorithm will be held in Fall 2005, with a publication to follow.
  
  
• Creation of standardized in vitro, in vivo and ex vivo assays and biological models, closely reflecting the molecular basis of human myeloma, to measure the effects of a given drug.

Clinical Trials and Correlative Sciences

• A Research Roundtable, conducted in partnership with the FDA and Dr. Rick Pazdur, Director of the FDA's Office of Oncology Drug Products, brought together industry, leading myeloma researchers, and regulatory officials to frame an optimal clinical trials design that would enable the faster approval of new myeloma therapies. A publication is forthcoming.
  
  
• Initiation of key correlative analyses by the MMRC to determine why a particular drug is or is not effective in a patient or subgroup of patients and to predict a patient's response to new and combination therapies.