-Author name in bold denotes the presenting author
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Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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705 The Burkitt Lymphoma International Prognostic Index (BL-IPI)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Front-Line Treatment and Prognostication of Burkitt Lymphoma, Plasmablastic Lymphoma, and DLBCL
Hematology Disease Topics & Pathways:
Adult, Diseases, Lymphoma (any), Non-Hodgkin Lymphoma, DLBCL, B-Cell Lymphoma, Lymphoid Malignancies, Study Population, Clinically relevant
Monday, December 7, 2020: 1:30 PM

Adam J Olszewski, MD1, Lasse H. Jakobsen, PhD2*, Graham P. Collins, MD, DPhil3, Kate Cwynarski4*, Veronika Bachanova, MD, PhD5, Kristie A. Blum, MD6, Kirsten M Boughan, DO7, Mark Bower, MD8*, Alessia Dalla Pria, MD9*, Alexey Danilov, MD10, Kevin A. David, MD 11, Catherine Diefenbach, MD12, Fredrik Ellin, MD, PhD13*, Narendranath Epperla, MD, MS14, Umar Farooq, MD15, Tatyana A. Feldman, MD16, Alina S. Gerrie, MD, MPH17, Deepa Jagadeesh, MD, MPH18, Manali Kamdar, MD, MDDS19*, Reem Karmali, MD, MSc20, Shireen Kassam, MBBS, FRCPath, PhD21*, Vaishalee P. Kenkre, MD22, Nadia Khan, MD23, Andreas Klein, MD24, Izidore S. Lossos, MD25, Matthew A. Lunning, DO, FACP26, Peter Martin, FRCPC, MD, MS27, Nicolas Martinex-Calle28*, Silvia Montoto, MD29, Seema Naik, MD30*, Neil Palmisiano, MD, MS31, David Peace, MD32, Elizabeth H Phillips, MBBS, BSc33*, Tycel J. Phillips, MD34, Craig A. Portell, MD35, Nishitha Reddy, MD36, Anna Santarsieri, MBBS37*, Maryam Sarraf Yazdy, MD38, Knut B. Smeland39*, Scott E. Smith, MD, PhD40, Stephen D. Smith, MD41, Suchitra Sundaram, MD42, Parameswaran Venugopal, MD43, Adam Zayac, MD44, Xiao-Yin Zhang, PhD45*, Catherine Zhu46*, Chan Yoon Cheah, MBBS47, Tarec Christoffer El-Galaly48 and Andrew M. Evens, DO, MMSc49

1Lifespan Cancer Institute, Warren Alpert Medical School of Brown University, Providence, RI
2Department of Haematology, Aalborg Unviersity Hospital, Aalborg, Denmark
3Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
4Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
5Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
6Winship Cancer Institute, Emory University, Atlanta, GA
7Adult Hematologic Malignancies & Stem Cell Transplant Section, University Hospitals Seidman Cancer Center, Cleveland, OH
8National Centre for HIV Malignancy, Chelsea & Westminster Hospital, London, United Kingdom
9Chelsea & Westminster Hospital, London, United Kingdom
10Toni Stephenson Lymphoma Center, City of Hope Comprehensive Cancer Center, Duarte, CA
11Cancer Institute of New Jersey, New Brunswick, NJ
12New York University School of Medicine, NYU Cancer Institute, New York, NY
13Department of Internal Medicine, Kalmar County Hospital, Kalmar, Sweden
14The Ohio State University James Comprehensive Cancer Center, Columbus, OH
15Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
16Hackensack University Medical Center, NY, NY
17BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada
18Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Solon, OH
19University of Colorado Cancer Center, Aurora, CO
20Division of Hematology Oncology, Northwestern University, Chicago, IL
21King's College Hospital, London, United Kingdom
22Carbone Cancer Center, University of Wisconsin, Madison, WI
23Fox Chase Cancer Center, Philadelphia, PA
24Division of Hematology and Oncology, Tufts Medical Center, Boston, MA
25Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL
26University of Nebraska Medical Center, Omaha, NE
27Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY
28Nottingham University Hospitals, Nottingham, GBR
29Department of Haemato-oncology, St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom
30Penn State Cancer Institute, Penn State Hershey Medical Center, Hershey, PA
31Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA
32Division of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL
33Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
34University of Michigan Comprehensive Cancer Center, Dexter, MI
35Division of Hematology/Oncology, University of Virginia, Charlottesville, VA
36Vanderbilt University Medical Center, Nashville, TN
37Department of Haematology, Cambridge University Hospitals NHSFT, Cambridge, United Kingdom
38Georgetown University Hospital, Washington, DC
39Department of Oncology, Oslo University Hospital, Oslo, Norway
40Loyola University Medical Center, Maywood, IL
41University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA
42Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
43Division of Hematology Oncology, Rush University Medical Center, Chicago, IL
44Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI
45Oxford University Hospitals, Oxford, GBR
46University College London Hospitals, London, United Kingdom
47Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia
48Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
49Rutgers Cancer Institute of New Jersey, Warren, NJ

Background. BL is a rare, high-grade B-cell lymphoma that is often studied in trials with small sample sizes. Historical definitions of “low-risk BL” vary between studies, use arbitrary cutoffs for lactate dehydrogenase (LDH), and identify a small favorable group, leaving >80-90% of patients (pts) in an undifferentiated “high-risk” category. A validated prognostic index will help compare study cohorts and better define good-prognosis pts for whom reduced treatment would be appropriate vs a poor-prognosis group in need of new approaches. Herein, we constructed and validated a simplified prognostic model for BL applicable to diverse clinical settings across the world.

Methods. We derived the BL-IPI from a large real-world evidence cohort of US adults treated for BL in 2009-2018 (Evens A, Blood 2020). Progression-free survival (PFS) from diagnosis until BL recurrence, progression, death, or censoring was the primary outcome. We first determined the best prognostic cutoffs for age, LDH (normalized to local upper limit normal, ULN), hemoglobin (Hgb), and albumin. Independent risk factors were ascertained by forward stepwise selection into Cox regression from candidate variables: age, sex, HIV+ status, ECOG performance status (PS) ≥2, advanced stage (3/4), involvement of >1 extranodal site, bone marrow, central nervous system (CNS), values of LDH, Hgb, and albumin. Derivation models used multiple imputation to mitigate bias from missing data and reported hazard ratios (HR) with 95% confidence interval (CI). BL-IPI groups, defined by inspection of survival curves, were compared using log-rank test for trend. We validated performance of the BL-IPI in an external retrospective dataset of BL pts treated contemporaneously in centers from the United Kingdom, Scandinavia, Canada, and Australia.

Results. Characteristics of pts in the derivation (N= 633) and validation (N=457) cohorts are shown in the Table. Age ≥40 years (yr), LDH >3xULN, Hgb <11.5 g/dL, and albumin <3.5 g/dL were determined as optimal prognostic cutoffs. Age ≥40 yr, PS ≥2, stage 3/4, involvement of marrow, CNS, LDH >3xULN, low Hgb, and low albumin were associated with inferior PFS in univariate tests. In the multivariable model age ≥40 yr, LDH >3xULN, PS ≥2, and CNS involvement were selected as 4 independent prognostic factors; adding stage did not enhance the model. The model was simplified to 3 groups with 0 (low risk; 18% of pts), 1 (intermediate risk; 36% of pts; HR=3.14; 95%CI, 1.61-6.14), or 2-4 factors (high risk; 46% of pts; HR=6.52; 95%CI, 3.48-12.20; Fig A) with 3 yr PFS of 92%, 72%, and 53%, respectively (P<.001, Fig. B); median PFS was reached only in the high-risk group (46 months, 95%CI, 19-53). BL-IPI was similarly prognostic for overall survival (OS, P<.001; Fig. C).

Among pts with stage III/IV (historically classified as “high-risk” and constituting 78% of all pts in the cohort), the BL-IPI further discriminated subgroups with 3 yr PFS of 87%, 71%, and 52%, respectively (P<.001; Fig. D), and OS of 95%, 75%, and 57%, respectively (P<.001; Fig. E). In addition, BL-IPI was prognostic regardless of HIV status, in the subcohort treated with rituximab (3 yr PFS: 92%, 73%, and 55%, respectively, P<.001), and among pts treated with specific regimens: CODOX-M/IVAC±R (3 yr PFS: 88%, 67%, 61%, respectively, P=.004), DA-EPOCH-R (3 yr PFS, 87%, 73%, 51%, respectively, P<.001), or hyperCVAD/MA±R (3yr PFS: 100%, 80%, 54%, respectively, P<.001).

In the international validation cohort, fewer pts had CNS involvement; most received CODOX-M/IVAC+R; and PFS/OS estimates at 3 yr were higher. BL-IPI categories were of similar size (low-risk 15%, intermediate-risk 35%, high-risk 50%), and provided similar risk discrimination (Harrell’s C=.65 in both datasets). PFS at 3 yr was 96%, 82%, and 63%, respectively (P<.001; Fig. F), and OS was 99%, 85%, and 64%, respectively (P<.001; Fig. G). In the validation cohort, BL-IPI remained prognostic in the subsets receiving rituximab (P<.001) and in advanced stage (P<.001).

Conclusions. BL-IPI is a novel prognostic index specific to BL, which was validated to allow for simplified stratification and comparison of risk distribution in geographically diverse cohorts. The index identified a low-risk group with PFS >90-95%, which could be targeted with future strategies for treatment de-escalation. Conversely, only about 55-60% of pts in the high-risk group achieved cure with currently available immunochemotherapy.

Disclosures: Olszewski: Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Jakobsen: Takeda: Honoraria. Collins: ADC Therapeutics: Consultancy, Honoraria; Celleron: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Research Funding; BeiGene: Consultancy; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; Pfizer: Honoraria; Celgene: Research Funding. Cwynarski: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau. Bachanova: Incyte: Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; FATE: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Danilov: Abbvie: Consultancy; BeiGene: Consultancy; Nurix: Consultancy; Celgene: Consultancy; Gilead Sciences: Research Funding; Takeda Oncology: Research Funding; Pharmacyclics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Astra Zeneca: Consultancy, Research Funding; Verastem Oncology: Consultancy, Research Funding; Karyopharm: Consultancy; Aptose Biosciences: Research Funding; Bristol-Myers Squibb: Research Funding; Rigel Pharmaceuticals: Consultancy. Diefenbach: Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; MEI: Research Funding. Epperla: Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Farooq: Kite, a Gilead Company: Honoraria. Feldman: Pfizer: Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Cell Medica: Research Funding; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Viracta: Research Funding; Trillium: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Eisai: Research Funding; Kyowa Kirin: Consultancy, Research Funding. Gerrie: AbbVie: Consultancy, Honoraria, Research Funding; Astrazeneca: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Sandoz: Consultancy. Jagadeesh: Regeneron: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; MEI Pharma: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees. Kamdar: BMS: Consultancy; Abbvie: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy; Seattle Genetics: Speakers Bureau. Karmali: BeiGene: Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; Karyopharm: Honoraria; AstraZeneca: Speakers Bureau; Takeda: Research Funding; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Khan: Seattle Genetics: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria; Bristol Myers Squibb: Research Funding; Celgene: Research Funding. Klein: Takeda: Membership on an entity's Board of Directors or advisory committees. Lossos: Verastem: Consultancy, Honoraria; Stanford University: Patents & Royalties; Seattle Genetics: Consultancy, Other; Janssen Biotech: Honoraria; NCI: Research Funding; Janssen Scientific: Consultancy, Other. Lunning: ADC Therapeutics: Consultancy; Legend: Consultancy; Acrotech: Consultancy; AstraZeneca: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding. Martin: Beigene: Consultancy; Regeneron: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; Kite: Consultancy; Incyte: Consultancy; Cellectar: Consultancy; Bayer: Consultancy; I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy. Martinex-Calle: Abbvie: Other: Travel grant. Naik: Celgene: Other: advisory board; Sanofi: Other: advisory board. Palmisiano: Genentech: Research Funding; AbbVie: Research Funding. Phillips: Beigene: Honoraria; Roche: Research Funding. Phillips: Seattle Genetics: Consultancy; Incyte: Consultancy, Other: travel expenses; AstraZeneca: Consultancy; Karyopharm: Consultancy; Beigene: Consultancy; Bayer: Consultancy, Research Funding; BMS: Consultancy; Pharmacyclics: Consultancy; Abbvie: Consultancy, Research Funding; Cardinal Health: Consultancy. Portell: Roche/Genentech: Consultancy, Research Funding; Infinity: Research Funding; Bayer: Consultancy; Amgen: Consultancy; TG Therapeutics: Research Funding; AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Xencor: Research Funding; BeiGene: Consultancy, Research Funding. Reddy: Celgene: Consultancy; BMS: Consultancy, Research Funding; Genentech: Research Funding; Abbvie: Consultancy; KITE Pharma: Consultancy. Yazdy: Abbvie: Consultancy; Genentech: Research Funding; Octapharma: Consultancy; Bayer: Honoraria. Smith: Bristol Meyers Squibb: Research Funding; Ayala: Research Funding; Seattle Genetics: Research Funding; Portola: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Incyte: Research Funding; Ignyta: Research Funding; Genentech: Research Funding; De Novo Biopharma: Research Funding; AstraZeneca: Consultancy; Millenium/Takeda: Consultancy; Beigene: Consultancy; Bayer: Research Funding; AstraZeneca: Research Funding; Acerta Pharma BV: Research Funding; Karyopharm: Consultancy. Cheah: Celgene, F. Hoffmann-La Roche, Abbvie, MSD: Research Funding; Celgene, F. Hoffmann-La Roche, MSD, Janssen, Gilead, Ascentage Pharma, Acerta, Loxo Oncology, TG therapeutics: Honoraria. El-Galaly: F. Hoffmann-La Roche: Current Employment, Other: Support of parent study and funding of editorial support. Evens: Research To Practice: Honoraria, Speakers Bureau; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

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