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5147 Impact of Maintenance Rituximab Following First-Line Systemic Therapy on Outcomes in Patients with Marginal Zone Lymphoma: Real-World Evidence from 10 US Centers

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster III
Hematology Disease Topics & Pathways:
Research, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Diseases, real-world evidence, Lymphoid Malignancies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Narendranath Epperla, MD, MS1, Kaitlin Annunzio, DO2, Geoffrey P. Shouse, PhD, DO3, Natalie S. Grover, MD4, Pallawi Torka, MD5, Marcus P Watkins, PhD6*, Andrea Carolina Anampa-Guzmán, MD7*, Timothy S. Oh, MD8*, Heather Reves, MS, BS9*, Montreh Tavakkoli, MD10, Emily Hansinger11*, Beth Christian, MD2, Colin Thomas, MD11, Stefan K. Barta, MD12, Praveen Ramakrishnan Geethakumari, MD, MS13, Reem Karmali, MD, MSc14, Nancy L. Bartlett, MD6 and Adam J Olszewski, MD15

1The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
2The James Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH
3City of Hope Comprehensive Cancer Center, Duarte, CA
4Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
5Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
6Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
7Roswell Park Comprehensive Cancer Center, Buffalo, NY
8Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
9Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern, Dallas, TX
10Department of Medicine, Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
11Thomas Jefferson University Hospital, Philadelphia, PA
12Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA
13Section of Hematological Malignancies and Cellular Therapy, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX
14Department of Medicine, Division of Hematology/Oncology and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Northwestern University Feinberg School of Medicine, Chicago, IL
15Brown University, Providence, RI

First-line treatment options for patients (pts) with marginal zone lymphoma (MZL) include rituximab monotherapy (R) and immunochemotherapy (IC), such as bendamustine with rituximab (BR) or RCHOP/RCVP. The efficacy of maintenance rituximab (M-R) has been studied in splenic (SMZL) and nodal (NMZL) MZL, showing a benefit in progression-free survival (PFS) when M-R is administered after BR (Rummel et al., ASCO 2018). However, the role of M-R in pts with extranodal MZL (EMZL) of the mucosa-associated lymphatic tissue (MALT), or those receiving R or RCHOP/RCVP, remains uncertain. In this study, we analyzed the outcomes of pts with MZL who received M-R after their first-line systemic therapy (R or IC) using data from a large multi-institutional retrospective cohort.

Adult pts with MZL (SMZL, NMZL, or EMZL) who were treated at 10 US medical centers from 2010 onwards were included. Pts who had received first-line treatment with either R or IC and achieved a partial (PR) or complete (CR) response to the initial therapy were divided into groups based on whether they subsequently received M-R or not. To avoid immortal-time bias, we required a minimum follow-up of 6 months from diagnosis. Outcomes included PFS, overall survival (OS) and cumulative incidence of histologic transformation (HT). Because of non-proportional hazards, Wilcoxon test was used to compare survival curves, and Cox models (augmented by multiple imputation to account for missing data) were bounded by 6 years of follow up. Multivariable models adjusted for prognostic factors including age, sex, performance status, stage, baseline hemoglobin, albumin, LDH, type of IC and CR/PR status at the end of therapy.

The study included 427 pts with a median age of 63 years. Of these pts, 53% were women, and 49% had EMZL, 27% had NMZL, and 23% had SMZL. The first-line therapies received were R (54%), BR (36%), RCHOP (7%), or RCVP (3%). A CR was achieved by 70% (n=298) of pts after the initial therapy. Overall, 33% (n=140) received M-R with a median of 8 cycles. Among pts who initially had PR, 39% converted to a CR during M-R therapy. The median follow-up period was 5 years.

Factors associated with a higher likelihood of receiving M-R included achieving a PR instead of a CR after the first-line therapy (41% vs 29% receiving M-R, respectively; p=0.02) and having the SMZL subtype (p=0.03, Fig 1A). Pts treated with RCHOP were less likely to receive M-R compared to those receiving other regimens (p=0.049). There was also evidence of hospital-level preference to either prescribe M-R or not.

We analyzed survival outcomes separately for pts who received first-line IC or R monotherapy, stratified further by MZL subtype and the type of IC regimen. Among pts who received IC (n=197), M-R was associated with longer PFS (median of 9.0 vs. 6.8 years, p=0.008, Fig 1B). However, the statistical significance was lost in the multivariable model (adjusted HR=0.52, 95%CI=0.25-1.10). When evaluated by MZL subtype, pts with EMZL had a significantly longer PFS with M-R (p=0.01), while those with NMZL and SMZL did not (p=0.41 and 0.10, respectively). When examining the type of first-line IC, pts receiving RCHOP/RCVP had a prolonged PFS with M-R (p=0.03), whereas the difference was not statistically significant after BR (p=0.12). There was no difference in OS overall (p=0.09; adjusted HR=0.55, 95%CI=0.12-2.60) or in any subgroup.

Among pts who received first-line R, there were no statistically significant differences in PFS (p=0.70; adjusted HR=0.99, 95%CI=0.59-1.66) or OS (p=0.17) based on the receipt of M-R, either in the entire cohort or any subset.

A total of 14 transformation events occurred during the study, including 3 in the M-R group. The cumulative incidence of HT did not significantly differ between the two groups (sub-HR=0.76, 95%CI=0.21-2.82, p=0.68).

In this large retrospective cohort study, the use of M-R in MZL was primarily influenced by local preferences, the quality of response after initial treatment, and the type of IC regimen. Receipt of M-R was associated with a longer PFS for pts receiving first-line IC, especially for those with EMZL and those receiving RCHOP/RCVP. These findings suggest a PFS advantage of M-R in EMZL, which is a novel observation. However, this advantage was not observed in terms of OS or the rate of HT. M-R after initial R did not show any significant differences in outcomes for MZL.

Disclosures: Epperla: Incyte: Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; 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; Beigene: Research Funding, Speakers Bureau. Shouse: Beigene, Inc.: Speakers Bureau; Kite Pharmaceuticals: Consultancy, Speakers Bureau. Grover: Kite: Honoraria; Genentech: Honoraria; Seagen: Honoraria; Caribou Biosciences: Honoraria; Tessa Therapeutics: Research Funding; Novartis: Honoraria; Sangamo: Current holder of stock options in a privately-held company; Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Honoraria. Torka: TG Therapeutics: Consultancy; Genmab: Consultancy; Seagen: Consultancy; Lilly USA: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy. Christian: F Hoffman-La Roche: Research Funding; BMS: Research Funding; Millenium: Research Funding; Acerta: Research Funding; Genentech: Research Funding. Barta: Acrotech: Consultancy; Affimed: Consultancy; Janssen: Consultancy; Daiichi Sankyo: Consultancy. Karmali: BeiGene: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria, Research Funding; Calithera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Morphosys: Consultancy, Speakers Bureau; Janssen: Consultancy. Bartlett: ADC Therapeutics, Foresight Diagnostics, Kite, F. Hoffmann-La Roche Ltd / Genentech, Inc., Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics, Autolus, BMS/Celgene, Forty Seven, Gilead/Kite Pharma, Janssen, Merck, Millennium, Pharmacyclics, F. Hoffmann-La Roche Ltd / Genentech, Inc., Seattle Genetics: Research Funding; Washington University School of Medicine: Current Employment. 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.

*signifies non-member of ASH