-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3380 Early Assessment of Treatment Response in Acute Myeloid Leukemia Using FLT PET/CT Imaging: A Trial of the ECOG-ACRIN Cancer Research Group (EAI141)

Program: Oral and Poster Abstracts
Session: 803. Emerging Diagnostic Tools and Techniques: Poster III
Hematology Disease Topics & Pathways:
AML, Diseases, Technology and Procedures, Myeloid Malignancies, imaging
Monday, December 7, 2020, 7:00 AM-3:30 PM

Robert Jeraj, PhD1*, Fenghai Duan, PhD2*, Ryan J. Mattison, MD3, Lale Kostakoglu, MD, MPH4*, Daniel A. Arber, MD5, Elisabeth Paietta, PhD6, Justin Romanoff, AM2*, Jennifer Holter-Chakrabarty, MD7*, Charles Arnold, MD8*, Stephen A. Strickland, MD9, Jennifer Whisenant, PhD10*, Barry Alan Siegel, MD11*, Geoffrey L Uy, MD12, Kebede H. Begna, MD13, Gregory Wiseman, MD14*, Aric C. Hall, MD15*, Scott Perlman, MD16*, Mark Litzow, MD13 and David Mankoff, MD, PhD17*

1Carbone Comprehensive Cancer Center, Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI
2Brown University, ECOG-ACRIN Biostatistical Center-Providence, Providence, RI
3Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI
4University of Virginia, Charlottesville, VA
5University of Chicago, Chicago, IL
6Cancer Center, Montefiore Medical Center, Bronx, NY
7Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
8University of Oklahoma Health Sciences Center, Oklahoma City, OK
9Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN
10Vanderbilt University, Nashville, TN
11Washington University St. Louis, Saint Louis, MO
12Washington University School of Medicine, Saint Louis, MO
13Division of Hematology, Mayo Clinic, Rochester, MN
14Diagnostic Radiology, Mayo Clinic, Rochester, MN
15Division of Hematology/Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
16Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI
17Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA

Introduction: Patients with acute myeloid leukemia (AML) are often treated with intensive induction chemotherapy to achieve complete remission (CR). Early response to standard anthracycline plus cytarabine induction (7+3) is assessed by a day 14 nadir bone marrow biopsy. The nadir marrow has limitations, though, including sampling issues and ambiguity as to whether blasts are leukemia cells vs. regenerating marrow. In prior studies, the predictive value for remission of the nadir marrow is only 67-84%. A more accurate predictor of residual disease (RD) would give clinicians an opportunity to modify therapy earlier. Positron emission tomography (PET/CT) with 3’-deoxy-3’-[18F]fluorothymidine (FLT) is a molecular imaging modality that can assess cellular proliferation in the bone marrow compartment. A prior single-institution pilot study showed a significant difference in the marrow FLT uptake between patients with AML who achieved CR and those who had RD after count recovery.

Methods: EAI141 was an ECOG-ACRIN-led, prospective, multi-center study designed to assess FLT PET/CT as a predictor of CR after AML induction. The primary objective was to evaluate the predictive value of post-treatment FLT PET/CT imaging for detecting RD, with the secondary objectives of evaluating the predictive value for detecting CR and estimating the sensitivity and specificity. Maximum standardized uptake value (SUVmax) of > 7 g/mL in total bone marrow compartment was chosen prospectively based on data from a pilot study as a marker for presence of leukemia cells at nadir. The predictive values, sensitivity, and specificity of the FLT PET/CT and the nadir bone marrow biopsy were calculated. Eligible subjects were 18 years or older with previously untreated AML who were to receive induction with 7+3. Subjects underwent a nadir marrow biopsy and an FLT PET/CT scan 10-17 days after starting induction, and prior to any re-induction if disease was noted on the nadir marrow. A recovery marrow was performed 28-35 days after initial treatment or re-induction to assess CR or RD. Subjects could undergo an optional pre-treatment scan. Relapse-free survival (RFS) and overall survival (OS) were additional clinical outcomes.

Results: 87 subjects from 9 centers were enrolled between 2016-2018, and 61 were considered evaluable. Reasons for being not evaluable included study ineligibility (n=3), no post-treatment scan (n=13), and no remission marrow (n=10). Median age was 58 years (range 21-73); 56% were men and 44% were women. CR was achieved in 56% (34/61). Treatment was a single induction course in 79% (48/61) and re-induction in 21% (13/61). Predictive value based on FLT PET/CT was 60% (9/15, 95% CI 32%-84%) for RD and 61% (28/46, 95% CI 45%-75%) for CR. Of patients who achieved CR, 28/34 had SUVmax ≤ 7 g/mL (sensitivity of 82%) and 9/27 of those who did not had high SUV­max > 7 g/mL (specificity 33%). Predictive value of an aplastic marrow was 59% (26/44) for CR and 56% (9/16) for RD. Of patients who achieved CR, 26/33 had marrow hypoplasia (sensitivity 79%) and 9/27 with RD had disease in the nadir marrow (specificity 33%). Significant heterogeneity of bone marrow compartment post treatment (SUVhetero ranging from 0.24 to 1.07) was observed in FLT-PET/CT scans. Heterogeneity of bone marrow compartment decreased about 50% from pre-treatment to post-treatment FLT PET/CT. OS for all participants, stratified by post-treatment FLT PET/CT response and nadir marrow results, are summarized in the Figure.

Conclusions: Although this study did not show significant advantage of FLT PET/CT compared to nadir marrow to predict RD or CR on the average, it did show signal heterogeneity in the study population that may be relevant to disease biology not appreciated by a single sampling site for the nadir or remission marrow. For example, in patients with false negative nadir biopsy, in approximately 20% of patients assessment with FLT PET/CT was correct, likely reflecting bone marrow heterogeneity and limitation of a single point sampling. Similarly, in almost 60% of patients with false positive nadir biopsy, FLT PET/CT assessment was correct.

Disclosures: Jeraj: AIQ Solutions: Current equity holder in private company. Kostakoglu: F. Hoffmann-La Roche: Consultancy. Strickland: KiTE: Consultancy; Kura: Consultancy; Astellas: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Sunesis: Research Funding; ArcherDx: Consultancy; AbbVie: Consultancy. Uy: Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Astellas Pharma: Honoraria. Perlman: GE Healthcare: Research Funding; AIQ: Research Funding.

*signifies non-member of ASH