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50 A Large Multicenter Real-World Evidence (RWE) Analysis of Autoimmune (AI) Diseases and Lymphoma: Histologic Associations, Disease Characteristics, Survival, and Prognostication

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Population data for Aggressive NHL Management
Hematology Disease Topics & Pathways:
Autoimmune Disorders, Lymphomas, Clinical Research, Diseases, Immune Disorders, Real World Evidence, Lymphoid Malignancies
Saturday, December 11, 2021: 9:45 AM

Jordan Carter, MD1, Adam J. Olszewski, MD2, Tatyana A. Feldman, MD3, Reem Karmali, MD, MSc4, Jean L. Koff, MD, MSc5, Sabarish Ayyappan, MBBS6, Matthew A. Lunning, DO, FACP7, Shazia Nakohda, MD8*, Nadia Khan, MD8, Aryeh Pelcovits, MD9, Jason Lofters, MD3*, Timothy Seijung Oh, MD4*, Colin Burke O'Leary, MA10*, Kittika Poonsombudlert, MD11, Carman Tong12*, Elaine Kuhn, MD13*, Mingen Liu, MD, PhD14*, Andrea Anampa-Guzman, MD15*, Megha Shalavadi, MD16*, Colin Thomas, MD17*, Melissa Kives18*, Ning C. Dong, MD19, Alexander Hershey, MD1*, Neil Palmisiano, MD20, Alexey V. Danilov, MD, PhD16, Francisco J. Hernandez-Ilizaliturri, MD21, Stefan K. Barta, MD, MRCP, MS22, Frederick Lansigan, MD13, Kerry J. Savage, MD, MSc, FRCPC23 and Andrew M. Evens, DO, MMSc1

1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
2Lifespan Cancer Institute, Alpert Medical School of Brown University, Providence, RI
3John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ
4Division of Hematology and Oncology, Northwestern University, Chicago, IL
5Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA
6Division of Hematology, Oncology and Blood and Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, IA
7Division of Hematology & Oncology, Department of Internal Medicine, University of Nebraska Medical Center- Fred and Pamela Buffett Cancer Center, Omaha, NE
8Fox Chase Cancer Center, Philadelphia, PA
9Lifespan Cancer Institute, Warren Alpert Medical School of Brown University, Providence, RI
10Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA
11Holden Comprehensive Cancer Center, University of Iowa Hospital and Clinics, Iowa city, IA
12Clinical Trials Unit, BC Cancer, Vancouver, BC, Canada
13Dartmouth-Hitchcock Medical Center, Lebanon, NH
14University of Pennsylvania, Philadelphia, PA
15Roswell Park Comprehensive Cancer Center, Buffalo, NY
16City of Hope Toni Stephenson Lymphoma Center, Duarte, CA
17Thomas Jefferson University, Philadelphia, PA
18Emory University, Atlanta, GA
19Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
20Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA
21Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
22Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
23BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada

Introduction: While an association between AI diseases and the development of lymphoma (LYM) is known, the impact of AI diseases on patient (pt) outcome across varying LYM subtypes, including the role of immunosuppressive medications (ISM), is not well understood.

Methods: We conducted a large, multicenter, RWE retrospective analysis of adult pts with a diagnosis (dx) of lymphoma (LYM) between 1/2000 and 12/2020 and a pre-existing AI disease (see full list AI in Table 1). We examined baseline clinical features at LYM diagnosis, underlying AI disease characteristics, type/duration of ISM, LYM therapy received and survival outcomes. Multinomial regression models adjusted for age and sex identified associations between LYM subtypes, AI diseases, and ISM exposure, and were reported as relative risk ratio (RRR). Survival rates were estimated by Kaplan-Meier. Univariate associations of baseline factors with survival in cases with non-missing data were examined by Cox model and stratified by International Prognostic Index (IPI).

Results: In total, 785 pts were identified across 14 North American institutions, of which 694 pts with complete data were included in the final analysis. Rheumatoid arthritis was the most common AI disease (30%) (Table 1). Diffuse large B-cell lymphoma (DLBCL) was the most common histologic subtype (n=303, 44%), and it was the most prevalent histology for nearly every AI disease. The median duration between AI disease and LYM diagnosis was 108 months (mo) (1-816 mo). Several associations were found between specific AI diseases and LYM subtypes, including: Hashimoto’s thyroiditis with marginal zone lymphoma (MZL, RRR 2.78 (95% CI 1.14-6.78, P=0.024), Waldenstrom’s macroglobulinemia (RRR 7.12 (95% CI 1.07-47.3, P=0.031), and follicular lymphoma (RRR, 2.71, 95% CI 1.01-7.24, P=0.047); Polymyalgia rheumatica with CLL/SLL (RRR 21.27 (95% CI 4.57-98.96), P=0.0001) and MZL (RRR 6.62 (95% CI 1.38-31.80), P=0.018); Psoriasis with peripheral T-cell lymphoma (PTCL, RRR 3.85 (95% CI 1.21-12.22), P=0.022); and Inflammatory bowel disease with CLL/SLL (HR 4.60 (95% CI 1.72-12.34), P=0.002).

Overall, 402 (58%) pts had ISM exposure prior to LYM dx, with 279 (40%) pts on active ISM at time of LYM dx. The most commonly used ISM agent was methotrexate (26%); the median duration of ISM prior to LYM diagnosis was 60 mo (1-480). Compared with DLBCL pts, those diagnosed with PTCLs were more likely to have had exposure to TNF-α inhibitors (RR 1.89, 95% CI 1.23-2.89, P=0.004) or apremilast, a phosphodiesterase-4 inhibitor (RR 19.2, 95% CI 2.6-149.9, P=0.005). Rituximab +/- chemotherapy was used as frontline therapy in the majority of B-cell LYM pts, including 90% of DLBCL. Of LYM pts on ISM at initial dx, 41% had a reduction in immunosuppression (RIS), of whom 81% stopped ISM completely (Table 1). Only 10% of pts who underwent RIS were reported to have a flare of AI disease during initial therapy, compared with 7% of pts who had a flare despite no RIS (P=NS).

Survival by histology is depicted in Figure A/B. For DLBCL pts (n=303), survival appeared overall comparable to historically reported outcomes in the general DLBCL population. Neither antecedent use of ISM nor duration of ISM were associated with pt outcomes (data not shown). However, a survival advantage was identified among DLBCL pts whose ISM was stopped completely during frontline therapy compared with pts who were not on ISM at diagnosis (Figure C/D). In addition, 10 DLBCL pts underwent 100% RIS +/- rituximab with therapeutic intent and did not receive cytotoxic chemotherapy as part of frontline therapy. Among these, 4 pts (mean age 62 years (26-84); ISM: n=2 MTX, and 1 each azathioprine and etanercept/MTX; EBV+ 2/4) achieved complete remission and remain disease-free at time of last follow-up at 5, 74, 105, and 221 months post-DLBCL dx.

Conclusions: Altogether, we identified several novel histologic associations of AI diseases with LYM histologic subtypes. Furthermore, prior receipt of TNF-α inhibitor or a phosphoediesterase 4 inhibitor were associated with a diagnosis of PTCL. For DLBCL pts with antecedent AI disease, complete cessation of ISM during frontline LYM therapy appeared to be associated with improved survival. Finally, there were a small number of select DLBCL pts who garnered long-term disease-free survival using RIS +/- rituximab as frontline therapy, similar to the treatment paradigm in post-transplant lymphoproliferative disorders.

Disclosures: Olszewski: TG Therapeutics: Research Funding; PrecisionBio: Research Funding; Celldex Therapeutics: Research Funding; Acrotech Pharma: Research Funding; Genentech, Inc.: Research Funding; Genmab: Research Funding. Feldman: Alexion, AstraZeneca Rare Disease: Honoraria, Other: Study investigator. Karmali: AstraZeneca: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Genentech: Consultancy; Janssen/Pharmacyclics: Consultancy; Epizyme: Consultancy; Karyopharm: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; EUSA: Consultancy; BeiGene: Consultancy, Speakers Bureau; BMS/Celgene/Juno: Consultancy, Research Funding; Takeda: Research Funding; Roche: Consultancy. Lunning: TG Therapeutics: Consultancy; Janssen: Consultancy; Verastem: Consultancy; Spectrum: Consultancy; Myeloid Therapeutics: Consultancy; AstraZeneca: Consultancy; Morphosys: Consultancy; ADC Therapeutics: Consultancy; Beigene: Consultancy; Daiichi-Sankyo: Consultancy; Kyowa Kirin: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; Legend: Consultancy; Acrotech: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy; Karyopharm: Consultancy; AbbVie: Consultancy. Palmisiano: Genentech: Research Funding; AbbVie: Consultancy, Research Funding; Takeda: Consultancy; Foundation One: Consultancy. Danilov: Bristol-Meyers-Squibb: Honoraria, Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TG Therapeutics: Consultancy, Research Funding; Takeda Oncology: Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Bayer Oncology: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria, Research Funding; SecuraBio: Research Funding; Rigel Pharm: Honoraria. Barta: Kyowa Kirin: Honoraria; Acrotech: Honoraria; Daiichi Sankyo: Honoraria; Seagen: Honoraria. Lansigan: Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Savage: Astra-Zeneca: Consultancy, Honoraria; Takeda: Other: Institutional clinical trial funding; Roche: Research Funding; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Seattle Genetics: Consultancy, Honoraria; Servier: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding.

*signifies non-member of ASH