We are international

Focus on Molecular Testing and Clinical Trials
By Brian G.M. Durie, M.D.

The IMF held its 3rd Scientific Advisors Retreat May 14th – 17th, 2004. A list of this year’s participants is provided at the end of this report. The goals this year were:

  1. Identify the most promising molecular targets for ongoing clinical research. Assess technology available for current research and future integration of appropriate tests in a clinical trial setting.
  2. Assess the most efficient ways to evaluate molecular endpoints within specific planned clinical trials. Discuss new response and treatment evaluation endpoints, such as time to progression.
  3. Review and attempt to prioritize trials involving novel agents to avoid duplication, and facilitate further comprehensive data analysis on an international scale.
  4. Evaluate the integration of molecular epidemiologic studies into cooperative group, institutional, and population-based studies. Consider development and implementation of appropriate questionnaires and data follow-up and analyses procedures.

The intent was to develop written summary recommendations for publication. It was anticipated that discussions would lead to updates to the recently published Myeloma Management Guidelines (The Hematology Journal [2003] 4, 379-398).

The retreat began with formal presentations covering gene expression profiling, DNA SNP analyses, and proteomics, and was followed by summaries of both U.S. and European myeloma clinical trials. In a separate session we covered a review of myeloma epidemiology and family studies, as well as an assessment of cytogenetic and FISH studies for bone marrow testing.

Thereafter, the participants broke into three groups in order to develop specific recommendations and plans:

Group 1: Chaired by Dr. Keith Stewart from Toronto , this group focused on current recommendations for molecular and genetic testing as part of trials as well as a “standard of care” approach. Members of the group felt strongly that a report should be prepared and published in order to provide firm guidance for both researchers and clinicians. This report is currently under development and will include details concerning:

  1. The need to collect and store bone marrow and tissue samples for analysis;
  2. That to the extent it is possible, collection and storage should be centralized;
  3. Academic institutions should take the lead in these endeavors, while collaborating closely with pharmaceutical partners and other interested parties;
  4. Establish a detailed “standard of care” recommendation for cytogenetic and FISH testing in clinical practice. Allow this to interface with ongoing validation and new discovery efforts;
  5. Attempt to develop specific treatment strategies for myeloma patients deemed to be at “high risk” based upon presence of chromosome 13 deletion and/or other molecular abnormalities;
  6. Validate and extend current molecular research findings. There is a pressing need to validate and extend observations on gene expression profiling on different data sets (e.g. other than the set from double autotransplant patients at UAMS). Other types of molecular testing should be encouraged including proteomics and SNP analysis.

Overall the recommendation is to develop a molecular basis for classifying and monitoring myeloma.

Group 2: Co-chaired by Dr. Dalsu Baris and Dr. Gareth Morgan, this group evaluated molecular testing and epidemiology. In essence, this group discussed the specific project details that are part of IMF’s Bank On A Cure™ program. Projects are being put in place to study both individual patients and patients as part of clinical trials, as well as patients and controls as part of a broader epidemiologic effort, including family studies. This was a helpful opportunity to discuss methodological issues, control populations, and other framework plans.

Group 3: Co-chaired by Dr. Brian Durie and Dr. Robert Kyle, this group focused on clinical trials and response/outcome evaluation. One of the main decisions was to proceed promptly to finish the pending manuscript dealing with new response criteria, which updates and extends the prior Bladé criteria. With ongoing input, this revised document will be ready for publication submission within a few weeks. This will be in line with the recent publications dealing with disease classification, management guidelines, and staging:

  1. The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Brit J of Haem 2003; 121: 749-757.
  2. Durie BGM, Kyle RA, et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hemat J 2003; 4: 379-398.
  3. Greipp PR, San Miguel J, Durie, BGM, et al. An International Staging System for Multiple Myeloma. Submitted.

Overall, the Bermuda retreat was a great success. Follow-up meetings and conference calls involving the complete International Myeloma Working Group will consolidate the new strategies.

Development of Recommendations for Molecular Testing in Clinical Trials
International Working Group Participants

Susie Novis International Myeloma Foundation (IMF) President
Brian G.M. Durie, MD Cedars- Sinai Comprehensive Cancer Center , USA
Robert A. Kyle, MD Mayo Clinic, USA
Dalsu Baris, MD, PhD National Cancer Institute, USA
Ross Brown, PhD MBA Royal Prince Alfred Hospital , AUSTRALIA
John Crowley, MD, PhD Cancer Research & Biostatistics , USA
Faith Davies University of Leeds, UK
Rafael Fonseca, MD Mayo Clinic, USA
Hartmut Goldschmidt , MD University of Heidelberg , GERMANY
Vania Hungria, MD Clinica Sao Germano, BRAZIL
Marco Ladetto, MD University of Torino, ITALY
Heinz Ludwig, MD, PhD Wilhelminenspital Der Stat Wien , AUSTRIA
Stephane Minvielle, MD, PhD Institute of Biology, Nantes , FRANCE
Gareth Morgan , MD , PhD The Royal Marsden Hospital , UK
Greg Mundy, MD University of Texas , San Antonio , USA
John Shaughnessy, PhD University of Arkansas Medical Sciences, USA
Keith Stewart, MD, PhD Princess Margaret Hospital CANADA
Brian Van Ness, PhD University of Minnesota , USA
Michael Barninger Novartis Oncology , USA
Thomas Cavanagh Celgene Corporation, USA
Dixie Esseltine Millennium Pharmaceuticals Inc. USA
Sean Maenpaa Celgene Corporation, USA
Lisa Paik IMF, USA
Joe Shaw IMF Bank On A Cure Director

 related articles