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382 Treatment Patterns and Outcomes for Patients with Classic Hodgkin Lymphoma (cHL) and Cardiomyopathy with Low Ejection Fraction (EF): Real-World Evidence (RWE) from 16 US Academic Centers

Program: Oral and Poster Abstracts
Type: Oral
Session: 905. Outcomes Research – Lymphoid Malignancies: Practice Changing Patient-Reported Outcome Measurements and Real World Evidence Studies in Patients With Lymphoma
Hematology Disease Topics & Pathways:
Research, Clinical Research, health outcomes research
Saturday, December 9, 2023: 4:45 PM

Kaitlin Annunzio, DO1, Eric McLaughlin, MS2*, Timothy Voorhees, MD, MSCR3, Lauren Kelly Shea, MD, MS4, Nuttavut Sumransub, MD5, Ashley Rose, MD6, Adam J Olszewski, MD7, Neil Bailey, MSc8*, Krish Patel8*, Tamara K. Moyo, MD9*, Farrukh T. Awan, MD10, Gulrayz Ahmed, MD, FACP11, Natalie S. Grover, MD12, Adam Adika, MD13*, Erica L Andres, MD14*, Muhammad Salman Faisal15*, Beth Christian, MD1, Jacob Anna16*, Steven M. Bair, MD17, Nicholas Kendsersky, MD18, Colin Thomas, MD18, Pallawi Torka, MD19, Jakub Svoboda, MD20, Jordan S Carter, MD13, Mehdi Hamadani, MD11, Hayder Saeed, MD6, Sanjal H. Desai, MBBS21, Andrew M Evens, DO, MBA, MMSc22 and Narendranath Epperla, MD, MS23

1The James Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH
2Center for Biostatistics, The Ohio State University, Columbus, OH
3Department of Hematology, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH
4O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
5Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN
6H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
7Brown University, Providence, RI
8Swedish Cancer Institute, Seattle, WA
9Atrium Health / Levine Cancer Institute, Charlotte, NC
10University of Texas Southwestern Medical Center, Dallas
11Medical College of Wisconsin, Milwaukee, WI
12Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
13Temple University Hospital, Philadelphia, PA
14University of Pennsylvania, Philadelphia, PA
15Roswell Park Cancer Center, Buffalo, NewYork, Buffalo, NY
16University of Colorado, Aurora, CO
17Division of Hematology, University of Colorado - Anschutz Medical Campus, Aurora, CO
18Thomas Jefferson University Hospital, Philadelphia, PA
19Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
20Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
21University of Minnesota, Saint Paul, MN
22Division of Blood Disorders, Rutgers Cancer Institute New Jersey, New Brunswick, NJ
23The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH

The cornerstone for management of newly diagnosed patients (pts) with cHL is an anthracycline (AC) based chemotherapy (chemo) regimen. There are a paucity of data available regarding treatment patterns and outcomes for cHL pts with low EF. Furthermore, cHL pts with low EF are typically excluded from clinical trials limiting our understanding on management of these pts.

This was a multicenter retrospective cohort study evaluating pts with newly diagnosed cHL with low EF from 16 US medical centers. Eligible pts included adults diagnosed after 1/1/2010 with pretreatment EF of <50% on echocardiogram. Pts who developed reduced EF during or after first-line treatment were excluded. Based on EF, pts were divided into 2 groups (gp): <45% (gp 1) and 45-49% (gp 2). First-line treatment was categorized into AC based and non-AC based therapies. Primary outcome was progression-free survival (PFS). Secondary outcomes included response rates to first-line therapy and overall survival (OS). Time to event endpoints were evaluated by Kaplan-Meier and Cox proportional hazard methods.

The study included 69 pts with a median age of 55 yrs (21-88), 74% males, and performance status (PS) of ECOG 0-1 in 65%. There were 37 (54%) pts in gp 1 and 32 (46%) in gp 2. 39 pts received AC and 30 received non-AC based therapies. Pts in the AC group were significantly younger (median age, 46 vs 64 yrs), had higher proportion with EF of 45-49% (72% vs 13%) & ECOG PS of 0-1 (82% vs 54%) compared to non-AC based therapies.

Among the 30 pts who received non-AC based therapies, 26 were in gp 1 and 4 in gp 2. Non-AC based therapies included BV monotherapy (n=6), non-AC BV-based therapies (n=11), and other non-AC chemo (n=13). The most common BV based therapy was BV+dacarbazine (n=4) followed by BV+bendamustine (n=3), while the most common other non-AC chemo was MOPP (n=4) followed by ChlVPP (n=3). The overall response rate (ORR) and complete response rate (CRR) to AC based therapy was 77% (30/39) and 69% (27/39), respectively. Among the non-AC therapies, the ORR/CR rates for BV monotherapy, BV based therapies, and other non-AC chemo were 33%/17%, 55%/27%, and 61%/54%, respectively.

The median PFS for the entire cohort was 2.7 yrs (95%CI= 0.80-5.01). The median PFS for gp 1 vs gp 2 was 1.55 yrs and 4.20 yrs, respectively (p=0.26). The median PFS was significantly longer in pts receiving AC based compared to non-AC therapies (5.01 yrs vs 0.55 yrs, <0.001, Figure 1) with 3- and 5-yr PFS estimates of 62% vs 27%, and 54% vs 16%, respectively. Among the recipients of non-AC therapies, the 3-year PFS estimates for BV monotherapy, BV based therapies, and other non-AC chemo was 20%, 34%, and 42%, respectively (p=0.25). The median OS for the entire cohort was 5.6 yrs (95% CI=3.47-NR). The median OS for gp 1 vs gp 2 was 5.41 yrs and 5.73 yrs, respectively (p=0.82). The median OS was significantly longer in pts receiving AC based compared to non-AC therapies (7.43 yrs vs 3.20 yrs, p=0.003) with 3- and 5-yr OS estimates of 80% vs 60% and 80% vs 30%, respectively. Among the recipients of non-AC therapies, the 3-year OS estimates for BV monotherapy, BV based therapies and other non-AC chemo were 44%, 78% and 51%, respectively.

Univariable Cox models tested baseline pt and disease variables and found increasing age, ECOG PS ≥2, and the presence of geriatric syndrome to be prognostic of inferior PFS and OS but not EF gp. Only increasing age remained associated with significantly inferior PFS and OS in multivariable analysis (Table 1). After adjusting for these variables together with the inclusion of first-line treatment (AC vs non-AC based therapies), we found first-line treatment with AC-based therapy was associated with superior PFS (aHR= 0.39, 95% CI=0.15-0.97, p=0.04) but not OS (aHR= 0.51 (95% CI=0.16-1.65, p=0.26, Table 1). With inclusion of treatment, only age remained associated with inferior OS in the multivariable adjustment (aHR=1.27, 95%CI=1.04-1.54).

This first RWE of cHL pts with low EF found that a majority of pts with EF of 45-49% were treated with AC-based therapies. Furthermore, PFS was improved for pts who received AC-based therapies. However, outcomes appeared modest for pts compared with expectant outcomes. Collectively, these data underscore the critical need for prospective interventional studies in this challenging pt population. Further data on AC dosing, safety, risk of AC-induced heart failure, etc. will be presented at the meeting.

Disclosures: Voorhees: Morphosys: Research Funding; Incyte: Research Funding; AstraZeneca: Research Funding; Novartis: Consultancy; Recordati: Consultancy, Research Funding. Olszewski: Leukemia & Lymphoma Society, Genetech, Inc. / F. Hoffmann-La Roche Ltd, Adaptive Biotechnologies, Precision Biosciences, Genmab: Research Funding; Genmab, Blue Cross/Blue Shield of Rhode Island, Schrodinger, ADC Therapeutics, BeiGene: Consultancy. Patel: AstraZeneca, Bristol Myers Squibb, Kite, TG Therapeutics: Speakers Bureau; Adaptive Biotechnelogies, AstraZeneca, Bristol Myers Squibb, CRISPR Therapeutics, Curis, Inc, Epizyme, Fate Therapeutics, Genentech, Inc. / F. Hoffmann-La Roche Ltd, Kite, Loxo Oncology, MEI Pharma, Merck, Nurix, Pharmacyclics/Janssen, Sunesis Pharmaceuti: Research Funding; Abbvie, ADC Therapeutics, AstraZeneca, BeiGene, Bristol Myers Squibb, Caribou Biosciences, Epizyme, Genentech, Inc. / F. Hoffmann-La Roche Ltd, Kite, Loxo Oncology, MEI Pharma, Merck, Morphosys, Nurix, Pharmacyclics/Janssen, Sana Biotechnology, TG Therape: Consultancy. Moyo: Kite Pharmaceuticals: Consultancy. Awan: Janssen, Gilead, Kite pharmaceuticals, Karyopharm, MEI Pharma, Verastem, Incyte, Johnson and Johnson, Merck, Epizyme, Loxo Oncology, Adaptive Biotechnologies, Genmab: Other: Consulting Agreements; Pharmacyclics LLC, an AbbVie Company.: Other: Contracted Research; AstraZeneca Pharmaceuticals LP: Other: Advisory Committee; AbbVie Inc, ADC Therapeutics, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol-Myers Squibb Company, Cardinal Health, Caribou Biosciences Inc, Celgene Corporation, Cellectar Biosciences Inc, DAVA Oncology, Epizyme Inc, Genentech, a member of the Roche: Other: Consulting Agreements. Grover: Sangamo: Current holder of stock options in a privately-held company; Novartis: Honoraria; Tessa Therapeutics: Research Funding; Caribou Biosciences: Honoraria; Seagen: Honoraria; Genentech: Honoraria; Kite: Honoraria; ADC Therapeutics: Consultancy, Honoraria; Seattle Genetics: Consultancy. Christian: F Hoffman-La Roche: Research Funding; BMS: Research Funding; Millenium: Research Funding; Acerta: Research Funding; Genentech: Research Funding. Torka: Genentech: Consultancy; Lilly USA: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Genmab: Consultancy; Seagen: Consultancy. Svoboda: Merck: Research Funding; TG Therapeutics: Research Funding; Incyte: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; ADCT: Consultancy; BMS: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Genmab: Consultancy; Pharmacyclics: Consultancy, Research Funding; Atara: Consultancy; SEAGEN: Consultancy, Research Funding. Hamadani: ADC therapeutics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Abbvie: Consultancy; Omeros: Consultancy; CRISPR: Consultancy; Genmab: Consultancy; Bristol Myers Squibb: Consultancy; Caribou: Consultancy; AstraZeneca: Speakers Bureau; Kite, a Gilead Company: Consultancy, Speakers Bureau; BeiGene: Speakers Bureau; Gamida Cell: Consultancy; Incyte: Consultancy; Genmab: Consultancy; Kadmon: Consultancy; Legend Biotech: Consultancy; MorphoSys: Consultancy; Novartis: Consultancy; SeaGen: Consultancy; Astra Zeneca: Speakers Bureau; BeiGene: Speakers Bureau; Sanofi Genzyme: Speakers Bureau; Astellas: Research Funding; Spectrum Pharmaceuticals: Research Funding; Takeda: Research Funding; Genentech: Honoraria; Myeloid Therapeutics: Honoraria. Saeed: Epizyme: Consultancy; Morphosis: Honoraria; Novarits: Consultancy. Desai: Seagen: Honoraria. Evens: Seattle Genetics: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Epperla: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH