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451 Outcomes of Patients with Limited-Stage Aggressive Large B-Cell Lymphoma with MYC Rearrangement with and without BCL2 and/or BCL6 Rearrangements: A Retrospective Analysis from 15 US Academic Centers

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: Population Based Outcomes in Aggressive Lymphoma
Hematology Disease Topics & Pathways:
Diseases, Adult, Non-Biological, Therapies, Lymphoma (any), DLBCL, chemotherapy, Study Population, Clinically relevant, Lymphoid Malignancies
Sunday, December 2, 2018: 4:30 PM
Ballroom 20D (San Diego Convention Center)

Shalin K. Kothari, MD1, Shaoying Li, MD2*, L. Jeffrey Medeiros, MD2, Emily C. Ayers, MD3, Daniel J. Landsburg, MD4, David A. Bond, MD5, Kami J. Maddocks, MD6, Anshu Giri, MD7*, Brian T. Hess, MD8, Luu Q. Pham9*, Ranjana H. Advani, MD9, Yang Liu, MD10*, Stefan Klaus Barta, MD, MRCP, MS11, Julie M. Vose, MD, MBA12, Michael C. Churnetski, BS13*, Jonathon B. Cohen, MD, MS14, Madelyn Burkart, MD15*, Reem Karmali, MD16, Joanna Zurko, MD17*, Amitkumar Mehta, MD17*, Adam J Olszewski, MD18, Sarah S Lee, MD19, Brian T. Hill, MD, PhD20,21, Timothy F. Burns, MD22, Frederick Lansigan, MD22, Emma Rabinovich, MD23*, David Peace, MD24, Adrienne Groman, MS25*, Kris Attwood, PhD, MS25*, Francisco J. Hernandez-Ilizaliturri, MD26 and Pallawi Torka, MD25

1Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
3University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA
4Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
5Divisions of Hematology and Medical Oncology, The Ohio State University Cancer Center, Columbus, OH
6Division of Hematology, Ohio State University Hospital, Columbus, OH
7Medical University of South Carolina, Charleston, SC
8Division of Hematology/Oncology; Hollings Medical Cancer Center, Medical University of South Carolina, Charleston, SC
9Stanford University, Stanford, CA
10Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA
11Fox Chase Cancer Center, Philadelphia, PA
12University of Nebraska Medical Center, Omaha, NE
13Winship Cancer Institute--Department of Hematology and Medical Oncology, Emory University, Atlanta, GA
14Winship Cancer Institute, Emory University, Atlanta, GA
15Northwestern University, Chicago, IL
16Division of Hematology, Northwestern University, Chicago, IL
17University of Alabama at Birmingham, Birmingham, AL
18Department of Medicine, Alpert Medical School of Brown University, Providence, RI
19Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
20Taussig Cancer Institute, Department of Hematology & Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH
21Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
22Dartmouth-Hitchcock Medical Center, Lebanon, NH
23University of Illinois at Chicago, Chicago, IL
24Division of Hematology/Oncology, University of Illinois College of Medicine, Chicago
25Roswell Park Comprehensive Cancer Center, Buffalo, NY
26Departments of Medicine and Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY

Introduction:

Patients (pts) with limited stage (LS) aggressive large B-cell lymphoma (ALBCL) comprise 30-40% of ALBCLs and are usually treated with R-CHOP with or without consolidative involved field radiation therapy (IFRT). In pts with ALBCL, cytogenetic studies have identified a subset with high-risk disease who harbor MYC rearrangement (MYC-R) with or without BCL2 (BCL2-R) and/or BCL6 (BCL6-R) rearrangements. This has led to the adoption of intensive induction strategies in this population; however, it is unclear if such an approach is necessary in limited stage disease.

Methods:

We conducted a multi-center (15 US academic centers) retrospective study of MYC-R LS-ALBCL pts with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) morphology. LS was defined by stage I and II confined to a single radiation field as determined by the treating center. Pts diagnosed between 1/1/2005 and 3/1/2017 were included. All pts received either R-CHOP or more intensive immuno-chemotherapy (IIC) (i.e. R-DA-EPOCH, R-hyperCVAD/MA, or R-CODOX-M/IVAC) with or without IFRT. Baseline demographic, clinical, laboratory, pathology and outcomes data was collected by retrospective chart review. Stage-modified IPI (sm-IPI) score was calculated [stage II (vs 1), age >60, elevated LDH, and ECOG performance status ≥ 2]. Differences in overall response rate (ORR), complete remission (CR) rate, 2-year progression-free survival (PFS) and overall survival (OS) were compared in pts treated with R-CHOP vs IIC and in pts treated with IFRT vs no IFRT.

Results:

A total of 142 pts with MYC-R LS-ALBCL were identified, of which 105 fulfilled the inclusion criteria. Baseline characteristics included: median age 65 yrs (range 21-85), 66% male; 14% stage I, 32% stage IE, 28% stage II, 26% stage IIE disease; 17% bulky, 58% extra-nodal, 15% transformed disease, 40% elevated LDH. The majority of pts (70%) had germinal center B-cell phenotype. Eighty-two pts had data on BCL2-R and BCL6-R, of which 41 (50%) had double-hit lymphoma (DHL), including 4 pts with triple-hit lymphoma.

Forty-five pts (43%) received R-CHOP, of which 56% had IFRT. Sixty pts (57%) received IIC, of which 42% had IFRT. R-DA-EPOCH was the most common IIC regimen used (85%), followed by R-hyperCVAD/MA (12%). Age (p=0.38), stage (p=0.32), extra-nodal disease (p=0.84), LDH (p=0.09), sm-IPI (p=0.24), morphology (p=0.44) and double-hit status (p=1.00) were similar between pts receiving R-CHOP and IIC. Median no. of cycles (NOC) (6 vs 6) and proportion of pts who received IFRT (56% vs 42%, p=0.17) did not differ in the 2 groups. Median NOC were lower in IFRT vs no IFRT group (4 vs 6; p=0.02). Pts receiving IIC (vs. R-CHOP) were more likely to undergo CNS prophylaxis (CNS-P) (75% vs 29%, p<0.001). No. of pts receiving CNS-P were similar in DHL vs MYC-R only (64% vs 49%; p=0.23).

ORR was 90% (83% CR, 7% PR). Pts with DHL were less likely to achieve a CR compared to pts with MYC-R only (73% vs 98%; p=0.011). CR rate was higher in the IFRT vs no-IFRT group (92% vs. 75%, p=0.028). In the 27 pts who had relapsed/refractory disease, distant relapses were more common in the IFRT vs no-IFRT group (87% vs 33%, p=0.007).

Median follow-up was 3.2 yrs; 35 (33%) pts progressed or died. Of the 23 deaths, 15 were due to progressive lymphoma, 1 due to treatment-related toxicity and 7 due to unrelated causes. 2-year PFS and OS were 78% and 86% for the entire cohort and 72% and 82% respectively for DHL pts. Sm-IPI ≥ 2 (HR: 2.81, p=0.02) and age ≥ 70 (HR: 4.07, P<0.001) were associated with inferior OS. Stage, extra-nodal disease, morphology, LDH and double hit status did not affect survival. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort (Figures 1 and 2) and in DHL pts (Figures 3 and 4). Use of CNS-P was not associated with improved PFS (HR: 0.57 [95% CI: 023, 1.43]) or OS (HR 0.98 [95% CI: 0.34, 2.85]).

Conclusions:

Outcomes of MYC-R LS-ALBCL pts are excellent with 2-year PFS and OS of 78% and 86% respectively. There was no benefit of choosing IIC over R-CHOP or using CNS prophylaxis in pts with MYC-R LS-ALBCL and LS-DHL in our study. While IFRT was effective in inducing CRs and preventing local relapses, distant relapses limited its benefit. Pts with LS-DHL had lower CR rates with similar PFS and OS when compared to those with MYC-R as the sole cytogenetic abnormality. Longer follow up is needed to assess the impact of upfront treatment strategies on late relapses.

Disclosures: Landsburg: Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Curis, INC: Consultancy, Research Funding. Maddocks: Teva: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria; Pharmacyclics/Janssen: Honoraria; Novartis: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; BMS: Research Funding; Bayer: Honoraria. Advani: Bayer Healthcare Pharmaceuticals: Other: Consultancy/Advisory Role; Cell Medica: Other: Consultancy/Advisory Role; Janssen Pharmaceutical: Other: Institutional Research Support; Regeneron Pharmaceuticals, Inc.: Other: Institutional Research Support; Merck: Other: Institutional Research Support; Kyowa: Other: Consulting/Advisory Role; Celgene: Other: Institutional Research Support; Roche/Genentech: Other: Consultancy/Advisory Role, Institutional Research Support; Takeda: Other: Consultancy/Advisory Role; Gilead/Kite: Other: Consultancy/Advisory Role; Autolus: Other: Consultancy/Advisory Role; AstraZeneca: Other: Consultancy/Advisory Role; Seattle Genetics: Other: Consultancy/Advisory role, Institutional Research Support; Bristol Myers Squibb: Other: Consultancy/Advisory role and Institutional Research Support; Forty Seven, Inc: Other: Institutional Research Support; Pharmacyclics: Other: Institutional Research Support; Agensys: Other: Institutional Research Support; Kura: Other: Institutional Research Support; Infinity: Other: Institutional Research Support; Millenium: Other: Institutional Research Support. Barta: Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Curis: Other: Travel support. Vose: Seattle Genetics, Inc.: Research Funding; Merck Sharp & Dohme Corp.: Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria; Roche: Honoraria; Epizyme: Honoraria; Kite Pharma: Research Funding; Celgene: Research Funding; Incyte Corp.: Research Funding; Bristol Myers Squibb: Research Funding; Acerta Pharma: Research Funding; Legend Pharmaceuticals: Honoraria. Cohen: Takeda: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioInvent: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Karmali: Gilead: Speakers Bureau; AstraZeneca: Speakers Bureau. Mehta: Seattle Genetics: Research Funding; Kite: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Speakers Bureau; Merck: Research Funding; Spectrum: Consultancy; Epizyme: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Incyte: Research Funding; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy; Carevive: Other: Patient engagement; Medpage: Other: Medical website. Olszewski: Spectrum Pharmaceuticals: Consultancy, Research Funding; TG Therapeutics: Research Funding; Genentech: Research Funding. Hill: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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