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706 Prognostication, Survival and Treatment-Related Outcomes in HIV-Associated Burkitt Lymphoma (HIV-BL): A US and UK Collaborative Analysis

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, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Lymphoid Malignancies, Study Population, Clinically relevant
Monday, December 7, 2020: 1:45 PM

Juan Pablo Alderuccio, MD1, Adam J Olszewski, MD2, Andrew M. Evens, DO, MMSc3, Graham P. Collins, MD, DPhil4, Alexey Danilov, MD5, Mark Bower, MD6*, Deepa Jagadeesh, MD, MPH7, Catherine Zhu8*, Amy Sperling, BS9*, Seo-Hyun Kim, MD10, Ryan Vaca, MD11, Catherine Wei12*, Suchitra Sundaram, MD13, Nishitha Reddy, MD14, Alessia Dalla Pria, MD15*, Christopher D'Angelo, MD16, Umar Farooq, MD17, David A. Bond, MD, BS18, Stephanie Berg, DO19, Michael C. Churnetski20*, Amandeep Godara, MD21, Nadia Khan, MD22, Yun Kyong Choi, MD23*, Shireen Kassam, MBBS, FRCPath, PhD24*, Maryam Sarraf Yazdy, MD25, Emma Rabinovich, MD26*, Frank Post27*, Gaurav Varma, MD, MPH28*, Reem Karmali, MD, MSc29, Madelyn Burkart, MD30*, Peter Martin, FRCPC, MD, MS31, Albert Ren32*, Ayushi Chauhan, MBBS, MD33, Catherine Diefenbach, MD23, Allandria Straker-Edwards, MS22*, Andreas Klein, MD34, Kristie A. Blum, MD35, Kirsten M Boughan, DO36, Agrima Mian, MBBS, MD37*, Bradley Haverkos, MD, MPH, MS38*, Victor M. Orellana-Noia, MD39, Vaishalee P. Kenkre, MD16, Adam Zayac, MD40, Seth M Maliske, MD17, Narendranath Epperla, MD, MS41, Paolo F Caimi, MD42, Scott E. Smith, MD, PhD43, Manali Kamdar, MD44, Parameswaran Venugopal, MD45, Tatyana A. Feldman, MD46, Daniel Rector47*, Stephen D. Smith, MD48, Andrzej Stadnik, MPH, BS49*, Craig A. Portell, MD50, Yong Lin, PhD12*, Seema Naik, MD51*, Silvia Montoto, MD52, Izidore S. Lossos, MD1 and Kate Cwynarski53*

1Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL
2Brown University, Providence, RI
3Rutgers Cancer Institute of New Jersey, Warren, NJ
4Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
5Toni Stephenson Lymphoma Center, City of Hope Comprehensive Cancer Center, Duarte, CA
6National Centre for HIV Malignancy, Chelsea & Westminster Hospital, London, United Kingdom
7Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Solon, OH
8University College London Hospitals, London, United Kingdom
9Fred Hutch Cancer Center, University of Washington, Seattle, UT
10Rush University Medical Center, Chicago, IL
11Penn State Cancer Institute, Penn State University College of Medicine, Hershey, PA
12Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
13Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
14Vanderbilt University Medical Center, Nashville, TN
15Chelsea & Westminster Hospital, London, United Kingdom
16Carbone Cancer Center, University of Wisconsin, Madison, WI
17Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
18Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
19Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL
20Winship Cancer Institute, Emory University Medical Center, Atlanta, GA
21Tufts Medical Center, Boston, MA
22Fox Chase Cancer Center, Philadelphia, PA
23New York University School of Medicine, NYU Cancer Institute, New York, NY
24King's College Hospital, London, United Kingdom
25Georgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC
26University of Illinois at Chicago, Cleveland Heights, OH
27King's College Hospital NHS Foundation Trust, London, United Kingdom
28Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY
29Division of Hematology Oncology, Northwestern University, Chicago, IL
30Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago
31Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY
32University of Illinois At Chicago, Chicago, IL
33Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC
34Division of Hematology and Oncology, Tufts Medical Center, Boston, MA
35Emory University, Atlanta, GA
36Adult Hematologic Malignancies & Stem Cell Transplant Section, University Hospitals Seidman Cancer Center, Cleveland, OH
37Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH
38University of Colorado Cancer Center, Aurora, CO
39Winship Cancer Institute, Emory University, Atlanta, GA
40Department of Medicine, Alpert Medical School of Brown University, Providence, RI
41The Ohio State University James Comprehensive Cancer Center, Columbus, OH
42University Hospitals of Cleveland, Cleveland, OH
43Loyola University Medical Center, Maywood, IL
44Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado Cancer Center, Denver, CO
45Division of Hematology Oncology, Rush University Medical Center, Chicago, IL
46Hackensack University Medical Center, NY, NY
47John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ
48University of Washington, Seattle, WA
49Knight Cancer Institute, Division of Hematology & Medical Oncology, Oregon Health & Science University, Portland, OR
50Division of Hematology/Oncology, University of Virginia, Charlottesville, VA
51Penn State Cancer Institute, Penn State Hershey Medical Center, Hershey, PA
52Department of Haemato-oncology, St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom
53Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom

Introduction: There are few data about prognostication and outcomes in patients (pts) with HIV-BL treated in the cART era. Optimal treatment strategies to minimize treatment-related mortality (TRM) remain unclear and current recommendations are based on small studies. We conducted a multicenter international analysis to identify prognostic factors and outcomes in pts with HIV-BL treated in the cART era.

Methods: This retrospective analysis included a subcohort from a recent study across 30 US sites (Evens et al. Blood 2020) augmented by data from 5 UK centers treated 2009-2018. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier & differences assessed by log-rank test. Univariate (UVA) associations were derived via Cox model and multivariable (MVA) models were constructed by forward selection of significant variables with P<0.05.

Results: 249 (US: 140 & UK: 109) pts with newly diagnosed HIV-BL were included. Clinical features included median age 43 (IQR 35-50 years [yrs]); male sex: 84%; ECOG PS: 2-4: 48%; elevated LDH: 85% (> 3x upper limit of normal (ULN) 49% & >5xULN 39%); >1 extranodal (EN) site: 60%; any CNS involvement (CNSinv) 25%; and +bone marrow (BM) 46%. MYC rearrangement was reported in 93% of pts with t(8;14) in 49%, break-apart probe in 41% and MYC-light chain in 3%; the rest had classical BL with negative MYC testing (4%) or missing result (3%) (otherwise classical BL). Median CD4 count was 217 (IQR 90-392 cells/µL) with 68% pts having CD4>100 cells/µL. At BL diagnosis, HIV viral load was detectable in 55%; 39% of pts were on cART. Baseline features were similar between the US & UK cohorts with significant differences only in ECOG PS 2-4 (32% vs 65%; P<0.001) & baseline CNSinv (30% vs 17%, respectively; P=0.02).

Tx regimens included: CODOX-M/IVAC (Magrath) 60%, DA-EPOCH 25%, HyperCVAD/MA 13%, & other 1%; most pts (87%) received rituximab (R). Similar regimens were used in pts with baseline CNSinv: Magrath 64%, DA-EPOCH 24% & HyperCVAD 12%. In the US, pts most frequently received DA-EPOCH (42%) followed by Magrath (32%) & HyperCVAD/MA (24%), whereas in the UK, 96% received Magrath. R was more frequently given in the US (94% vs 79%, P<0.001). Similar baseline features were seen in US pts selected for DA-EPOCH as those selected for Magrath or HyperCVAD/MA except for lower median CD4 count (144 vs 260 cells/µL; P=0.04). Overall response to Tx was: CR 70%, PR 9%, PD 14%, not evaluable 7%. TRM was 18% following HyperCVAD/MA, 13% after DA-EPOCH & 7% in patients treated with Magrath. Overall, 33% of pts had a relapse of HIV-BL with 23% systemic only & 10% CNS.

With median follow-up of 4.5 yrs, 3-yr PFS & OS were 61% & 66%, respectively, and nearly identical in both countries (Fig A). Pts with CD4>100 cells/µL had better 3-yr PFS (Fig B) & OS (68% vs 57% P=0.03). We observed significantly worse outcomes in pts with baseline CNSinv (3-yr PFS 36% vs 69%, P<0.001; OS 41% vs 73%, P<0.001; Fig C). Magrath was associated with the highest 3-yr PFS (66%) compared with 63% after HyperCVAD/MA & 51% after DA-EPOCH, but the difference was not significant (P=0.13; Fig D). Pts receiving R had numerically higher PFS, but also not statistically significant (63% vs 53% P=0.16). We observed poor outcomes in pts with baseline CNSinv regardless of frontline Tx (3-yr PFS HyperCVAD/MA 40%, Magrath 39%, DA-EPOCH 32%; P=0.93; Fig E).

The incidence of CNS recurrence at 3 yr across all Tx was 11%. Higher incidence was observed with DA-EPOCH (P=0.032 vs other regimens; Fig F) with no difference according to CD4 count. Variables associated with PFS & OS on UVA included: ECOG PS 2-4, >1 EN, +BM, baseline CNSinv, LDH>ULN, CD4 <100 cells/µL. On MVA, the variables independently associated with inferior PFS were ECOG PS 2-4 (HR 1.87 P=0.007); baseline CNSinv (HR 1.70, P=0.023); LDH >5xULN (HR 2.09, P<0.001); and >1 EN sites (HR 1.58 P=0.043). The same variables were significant on MVA for OS. Adjusting for all of the prognostic variables, Tx with Magrath was associated with longer PFS (adjusted HR, 0.45, P=0.005).

Conclusions: These data represent the largest analysis of HIV-BL to date. There were favorable tolerance and outcomes with intensive R-containing regimens with Magrath being associated with lower TRM and the highest PFS. In addition, prognostic factors for pt outcomes were associated with lymphoma characteristics rather than with HIV-related features. Pts with baseline CNSinv represent a high-risk group with unmet therapeutic needs.

Disclosures: Alderuccio: Oncinfo: Honoraria; Puma Biotechnology: Other: Family member; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member. Olszewski: Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding. Evens: Epizyme: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Collins: Gilead: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; BeiGene: Consultancy; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; Celleron: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Celgene: Research Funding; Amgen: Research Funding; Pfizer: Honoraria. Danilov: Astra Zeneca: Consultancy, Research Funding; Verastem Oncology: Consultancy, Research Funding; Takeda Oncology: Research Funding; Gilead Sciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Nurix: Consultancy; Celgene: Consultancy; Aptose Biosciences: Research Funding; Bristol-Myers Squibb: Research Funding; Rigel Pharmaceuticals: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Consultancy; BeiGene: Consultancy; Abbvie: Consultancy. Jagadeesh: 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; Regeneron: Research Funding. Reddy: Genentech: Research Funding; Abbvie: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy. Farooq: Kite, a Gilead Company: Honoraria. Bond: Seattle Genetics: Honoraria. Khan: Celgene: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding. Yazdy: Bayer: Honoraria; Genentech: Research Funding; Octapharma: Consultancy; Abbvie: Consultancy. Karmali: Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Takeda: Research Funding. Martin: Incyte: Consultancy; Regeneron: Consultancy; Celgene: Consultancy; Bayer: Consultancy; Cellectar: Consultancy; Beigene: Consultancy; I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy; Morphosys: Consultancy; Kite: Consultancy. Diefenbach: Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; MEI: Research Funding; LAM Therapeutics: Research Funding; Incyte: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Denovo: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Klein: Takeda: Membership on an entity's Board of Directors or advisory committees. Haverkos: Viracta THerapeutics: Consultancy. Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Caimi: Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding; Celgene: Speakers Bureau; Verastem: Other: Advisory Board. Kamdar: Roche: Research Funding. Feldman: Eisai: Research Funding; Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Trillium: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Viracta: 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; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Smith: AstraZeneca: Consultancy; Millenium/Takeda: Consultancy; Karyopharm: Consultancy; Beigene: Consultancy; Seattle Genetics: Research Funding; Ayala: Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Acerta Pharma BV: Research Funding; Bristol Meyers Squibb: 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. Portell: Amgen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; Janssen: Consultancy; TG Therapeutics: Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Xencor: Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding. Naik: Celgene: Other: advisory board; Sanofi: Other: advisory board. Lossos: Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Stanford University: Patents & Royalties; NCI: Research Funding; Seattle Genetics: Consultancy, Other; Janssen Scientific: Consultancy, Other. Cwynarski: 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; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau.

*signifies non-member of ASH