Implications of Serial Magnetic Resonance Imaging and Positron Emission Tomography Scanning for Survival of Untreated Myeloma Patients Treated with Total Therapy 3

Abstract

Abstract 3082 Introduction:We have previously reported on the prognostic implications of state-of-the-art imaging with magnetic resonance imaging (MRI) in Total Therapy 2 and with fluoro-deoxy-glucose positron emission tomography (PET) in Total Therapy 3 (TT3). With both techniques, baseline focal bone lesion number and reduction and resolution of focal lesions (FL) imparted favorable clinical outcomes. Here we are updating both MRI and PET data as they pertain to survival of patients enrolled in TT3A protocol employing VTD (bortezomib, thalidomide, dexamethasone), now with longer follow-up of 6.2 yr compared to 3.6 yr at the time of original publication. The details of the protocol and clinical outcomes have been reported previously. Methods: Analyses were restricted to 239 truly untreated patients in TT3A, as even one cycle of prior therapy pertaining to 64 patients had been shown to alter PET results. Cox regression modeling was employed for overall survival (OS) and progression free survival (PFS). Results: OS and PFS were adversely affected by the presence of FL number at baseline, whether defined by MBS (p<0.0001 and p=0.0009, respectively), MRI (p=0.03 and p=0.03, respectively), or PET (p<0.0001 and p<0.0001, respectively); in addition, extra-medullary disease (EMD) detected by PET especially affected OS (78% vs 43%, p=0.003) and PFS (73% vs 29%, p=0.003) unfavorably. In the context of GEP-defined 70-gene risk model (GEP70), FL number distinguished significantly poorer outcomes in low-risk myeloma whereas, for high-risk disease, only a trend was observed (Figure 1A).Complete FDG suppression prior to first transplant affected subsequent OS and PFS favorably (Figure 1B), especially in the GEP-70-defined high-risk subset so that such patients fared almost as well as the low-risk group (Figure 1C). Earlier FDG suppression by day 7 of induction therapy also favorably affected the OS (84% vs 78%, p=0.05). In multivariate analysis, >3 PET lesions featured with poorer OS (HR=1.98 95%CI, p=0.011) and PFS (HR=1.78, 95%CI, p=0.021). Conclusions: The data presented herein, confirm and extend the previously reported results on the role and utility of MRI and PET imaging in the diagnosis and management of newly diagnosed multiple myeloma. Presence of MM lesions on MRI & PET, presence of EMD and failure of FDG suppression with induction chemotherapy and transplantation carry adverse outcome and can serve as prognostic indicators of long-term survival. FDG suppression after first transplant was especially significant in further distinguishing the poor responders within the GEP70-defined high-risk myeloma. [Display omitted] Disclosures:Barlogie:Celgene, Genzyme, Novartis, Millennium: Consultancy, Honoraria, Patents & Royalties.