Gene Expression Profiling of Bone Marrow Biopsy in Multiple Myeloma Patients Under Treatment Helps Define Duration of Maintenance Therapy

• Activity Number: 194
• Type: Contributed
• Date/Time: Monday, August 5, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Pingping Qu*+ and Christoph Heuck and Qing Zhang and Antje Hoering and Joshua Epstein and Bart Barlogie and John Crowley
• Companies: Cancer Research And Biostatistics (CRAB) and University of Arkansas for Medical Sciences and University of Arkansas for Medical Sciences and Cancer Research And Biostatistics and University of Arkansas for Medical Sciences and University of Arkansas for Medical Sciences and Cancer Research And Biostatistics
• Keywords: multiple myeloma ; gene expression profiling ; micro-environment ; complete remission ; maintenance therapy ; normalization

Abstract

Multiple myeloma (MM) is characterized by malignant plasma cells that reproduce uncontrollably. It is well established that the bone marrow micro-environment (ME) that plasma cells adhere to plays an important role in MM survival and progression. Although complete response (CR, as measured by normalization of plasma cell output) has been linked to survival, it does not provide guidance regarding duration of maintenance therapy. An important question in MM research is if and when to stop maintenance therapy for patients in CR. Towards this end, we compared GEP ME samples from normal donors and MM patients at baseline and established a gene signature to characterize whether a patient's ME profile was similar to that from a normal donor. Using such a signature, patients in CR were evaluated and classified as normalized or failed to normalize. Importantly, those normalized patients exhibited superior survival compared to those not normalized. We also tested the gene signature in long-term (>10 years) survivors and found more than half were normalized. We concluded that GEP of the bone marrow ME in MM provides insight as to when to stop therapy in the maintenance stage of treatments.