Prognostic Significance of Tracking Dynamic Changes in Positron Emission Tomography (PET) Scan Pre and Post Autologous Stem Cell Transplant (ASCT)
Authors: Atrash Shebli , Robinson Myra M , Bhutani Manisha , Slaughter Daniel , Hamadeh Issam S. , Voorhees Peter M. , Eddy Jill , Minard Lauren , Freind Reed , Robinson Jordan , AMI NDaiye , Sprouse Chelsea , Symanowski James , Khan Maham , Avalos Belinda Rene , Banderudrappagari Rajesh , Arnall Justin , Copelan Edward A. , Usmani Saad Z. 
Published: October 2019

Abstract
BACKGROUND:
Multiple Myeloma (MM) is a heterogenous disease with variable outcomes based on both disease biology and burden. The revised international staging system (R-ISS) can distinguish 5-year overall survival (OS) however, it does not incorporate novel imaging that provide more accurate disease burden assessment (e.g., PET-CT). Previous studies (Usmani SZ et al Blood 2013) showed that the presence of more than 3 focal lesions (FL)s detected on PET-CT scan at baseline in newly diagnosed MM patients, or the persistence of any FL post induction therapy or post- autologous stem cell transplantation (ASCT), were associated with shorter progression free survival (PFS) and overall survival (OS) in Total Therapy trials. There is limited information available on the prognostic significance of PET-CT in the context of current standard 3-drug induction followed by ASCT in clinical practice. Herein, the investigators examined the prognostic implications of post-therapy PET-CT positivity in routine clinical practice.
PATIENTS AND METHODS:
The LCI MM database was interrogated (3/2014-5/2018) for NDMM patients who had undergone upfront ASCT and had PET-CT data available. Continuous variables were summarized with descriptive statistics, while categorical variables were summarized with frequencies and proportions. Survival distributions were estimated with Kaplan Meier techniques and compared using a log rank test PET-CT scan results were reported as negative or positive (defined as one FL having higher 18F-FDG uptake relative to uptake in mediastinum or surrounding background, with no similar activity seen on the contralateral side, or increased activity at any location incompatible with normal physiological distribution).
RESULTS:
A total of 198 MM patients were identified, 62 had pre-ASCT PET-CT scans and 80 patients had post-ASCT PET-CT. Median age at transplant was 62 years (range 25 - 77), 52.0% were female. R-ISS stage I (17.2%), stage II (41.4%), stage III (1.7%). The 3 years overall survival (OS) in patients with negative PET-CT post-ASCT vs. positive PET-CT post-ASCT was 96.6% vs. 74.2% (p-value 0.002) and median progression free survival (PFS) was 35 months vs. 13 months (p-value <0.001), respectively. Patients were then divided into three groups: Cohort 1- negative PET scan pre/post ASCT (n=35), cohort 2- positive PET-CT pre-ASCT/negative PET-CT post-ASCT(n=17), and cohort 3- positive PET-CT post-ASCT(n=6). Thirty-four patients had scans pre and post ASCT; an additional n = 24 had negative PET scans pre ASCT and did not require repeat PET scan post ASCT. At one-year landmark OS for cohort-1 was 100% vs cohort-2 100% vs cohort-3 66.7 (p-value 0.002). One-year PFS for cohort-1 92.5% vs. cohort-2 100% vs. cohort-3 66.7% (p-value 0.0513).
CONCLUSIONS:
Negative PET-CT imaging post ASCT is associated with better OS and PFS. Also, in our population, the absence of positive FL by PET-CT scan in newly diagnosed MM patients pre and post ASCT shows a trend towards better PFS and OS. Clearance of FL by PET scan trends towards improved PFS and OS. Longer follow up is needed to declare statistical significance between those cohorts.
Figure. Figure.

Disclosures
Atrash: Takeda Oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Voorhees:Amgen Inc.: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; Novartis: Consultancy, Other: served on an IRC; TeneoBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees. Usmani:Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding; Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy.