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4207 Predictive Value of Staging PET/CT to Detect Bone Marrow Involvement in Marginal Zone Lymphoma (MZL): An Analysis from LEO MZL Working Group

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, adult, epidemiology, Clinical Practice (Health Services and Quality), Lymphomas, elderly, Clinical Research, Diseases, indolent lymphoma, clinical procedures, Lymphoid Malignancies, young adult , Technology and Procedures, Study Population, Human, imaging
Monday, December 12, 2022, 6:00 PM-8:00 PM

Juan Pablo Alderuccio, MD1, Isildinha M Reis, PhD2*, Jean L. Koff, MD, MSc3, Melissa C. Larson, MS4*, Dai Chihara, MD5, Wei Zhao, MD, MS6*, Sara Haddadi7*, Thomas M. Habermann, MD8, Peter Martin, FRCPC, MD, MS9, Jennifer R Chapman-Fredricks, MD10*, Christopher Strouse, MD11, Brad S. Kahl, MD12, Jonathon B. Cohen, MD, MS13, Jonathan W. Friedberg, MD, MMSc14, James R. Cerhan, MD, PhD4, Christopher R. Flowers, MD15 and Izidore S. Lossos, MD16

1Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
2Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
3Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA
4Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
5Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
6Division of Biostatistics, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
7Sylvester Comprehensive Cancer Center, Miami
8Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN
9Meyer Cancer Center, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY
10/Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
11Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
12Division of Oncology, Washington University School of Medicine in St. Louis, Saint Louis, MO
13Department of Hematology and Medical Oncology, Emory University, Atlanta, GA
14James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY
15Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX
16Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL

Introduction: Bone marrow (BM) involvement impacts stage and prognosis in lymphoma, remaining an important factor in risk-stratification scores, including the MALT-IPI. PET/CT is routinely implemented in the staging and response assessment of patients with lymphoma. However, FDG avidity to detect marginal zone lymphoma (MZL) remains debatable. In this study we aimed to assess the predictive value of PET/CT to detect BM involvement and survival implications in MZL using prospectively collected data from the Lymphoma Epidemiology of Outcomes (LEO) cohort.

Methods: The LEO cohort is a prospective cohort from 8 academic cancer centers in which patients are enrolled within 6 months of lymphoma diagnosis and followed. We extracted baseline data of MZL patients enrolled in the LEO cohort between 5/2015 and 2/2020. BM biopsy was used as a gold standard for BM involvement. In addition, radiology reports were reviewed for PET/CT-suggested BM involvement. Event-free survival (EFS) defined as time from diagnosis to relapse/progression, retreatment, or death due to any cause and overall survival (OS) defined as time from diagnosis to death due to any cause were estimated by Kaplan-Meier.

Results: Of 706 MZL patients enrolled in LEO, 311 (44%) with data on BM status by both biopsy and PET/CT were included in the analysis. Patients’ characteristics were median age 64 (range 24-89) years with most <70 years (n=217, 69.8%), non-Hispanic (n=264, 84.9%) white (n=276, 88.7%), without B symptoms (n=246, 79.1%), and normal LDH (n=185, 59.5%). The most common MZL subtype was extranodal (EMZL, n=208, 66.9%) followed by nodal (NMZL, n=61, 19.6%) and splenic (SMZL, n=42, 13.5%). Stage distribution was as follows: early-stage (I-II; n=134, 43.1%), advanced-stage (III-IV; n=159, 51.1%), and unknown (n=18, 5.8%). BM biopsy was positive in 99 (31.8%) and negative in 212 (68.2%) patients.

Across all MZL subtypes, biopsy-proven and PET/CT-suggested BM involvement was present in 11.6% (n=36/311), and positive BM biopsy with negative PET/CT was observed in 20.3% (n=63/311) (EMZL=9.6%, n=20/208; NMZL=31.1%, n=19/61; and SMZL=57.1%, n=24/42). For EMZL, 15.9% (n=33) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 39.4% (n=13) and negative in 60.6% (n=20). For NMZL, 50.8% (n=31) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 38.7% (n=12) and negative in 61.3% (n=19). Most patients (83.3%, n=35) with SMZL demonstrated pathologically confirmed BM involvement, with positive PET/CT in 31.4% (n=11) and negative in 68.6% (n=24). Considering BM result from biopsy as the standard, PET/CT-based sensitivity and specificity in EMZL, NMZL, and SMZL were 39.4% & 98.9%, 38.7% & 100%, and 31.4% & 100%, respectively. PET/CT-based positive and negative predictive values in EMZL, NMZL, and SMZL were 86.7% & 89.6%; 100% & 61.2%; and 100% & 22.6%, respectively.

With a median follow up of 35.4 months there were 70 EFS events and 18 OS events across all MZL subtypes. The 2-year EFS and OS were 81.7% (95%CI 76.8-85.7%) and 96.8% (95%CI 93.9-98.3%), respectively. The 2-year EFS and OS by histology were EMZL= 84.7% (95%CI 78.7-89.1%) & 97.2% (95%CI 93.5-98.8%); NMZL= 69.6% (95%CI 56.1-79.6%) & 96.5% (95%CI 86.9-99.1%); and SMZL= 85.6% (95%CI 70.7-93.3%) & 95.2% (95%CI 82.3-98.8%), respectively. Acknowledging the low number of events and unspecific criteria for treatment selection, those patients exhibiting pathological BM involvement (n= 99) did not show significantly different EFS (p=0.097) (EMZL p=0.48; NMZL p=0.68; and SMZL p=0.75, respectively) or OS (p=0.978) (EMZL p=0.46; NMZL=0.53; and SMZL=0.21, respectively) compared to those without BM disease.

Conclusions: While PET/CT may be positive in nodal and some extranodal locations, assessment of BM involvement by PET/CT is characterized by a low sensitivity across all MZL subtypes and low negative predictive value in SMZL, underscoring the limitations of current Lugano criteria in staging MZL. With currently relatively limited follow-up, we did not observe significantly different survival based on BM status.

Disclosures: Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Pyramid: Consultancy; Agios: Consultancy. Koff: Atara BioTherapeutics: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Oncternal Therapeutics: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Viracta Therapeutics: Research Funding. Chihara: Eisai: Honoraria; AstraZeneca: Honoraria. Martin: ADCT: Consultancy; AstraZeneca: Consultancy; Beigene: Consultancy; BMS: Consultancy; Daiichi Sankyo: Consultancy; Epizyme: Consultancy; Genentech: Consultancy; Janssen: Consultancy; Regeneron: Consultancy; Takeda: Consultancy. Kahl: AstraZeneca: Consultancy, Research Funding; ADT Therapeutics: Consultancy; Roche: Consultancy; Genentech: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; MEI: Consultancy; AcertaPharma: Consultancy; Pharmacyclics: Consultancy; Celgene/BMS: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Kite: Consultancy; Janssen: Consultancy; Incyte: Consultancy; Hutchmed: Consultancy, Research Funding; Seattle Genetics: Consultancy; TG Therapeutics: Consultancy; Genmab: Consultancy; Research To Practice: Speakers Bureau. Cohen: Aptitude Health: Consultancy; Kite Pharma/Gilead: Consultancy; BMS/Celgene: Research Funding; Lilly Oncology/Eli Lilly: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Janssen: Consultancy; Takeda: Research Funding; Genentech: Research Funding; HutchMed: Consultancy, Research Funding; Astrazeneca: Consultancy, Research Funding; Novartis: Research Funding. Cerhan: NanoString: Research Funding; GenMab: Research Funding; Genentech: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Protagonist: Membership on an entity's Board of Directors or advisory committees. Flowers: Iovance: Research Funding; Cellectis: Research Funding; EMD: Research Funding; Guardant: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; Ziopharm: Research Funding; Denovo Biopharma: Consultancy; Genmab: Consultancy; V Foundation, Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; National Cancer Institute: Research Funding; Spectrum: Consultancy; Janssen Pharmaceutical: Research Funding; Amgen: Research Funding; Allogene: Research Funding; Adaptimmune: Research Funding; Kite: Research Funding; Morphosys: Research Funding; Acerta: Research Funding; NPower: Current holder of stock options in a privately-held company; Takeda: Research Funding; Sanofi: Research Funding; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; BeiGene: Consultancy; Genentech/Roche: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; SeaGen: Consultancy; Celgene: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; TG Therapeutics: Research Funding; Pharmacyclics/Janssen: Consultancy; Abbvie: Consultancy, Research Funding; Karyopharm: Consultancy; 4D: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Pfizer: Research Funding. Lossos: NCI: Research Funding; Adaptive: Honoraria; LRF: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH