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170 Impact of Monoclonal Protein at Diagnosis on Outcomes in Patients with Marginal Zone Lymphoma: A Multicenter Cohort Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 905. Outcomes Research—Lymphoid Malignancies: Health Outcomes in Plasma Cell Disorders and Transplant
Hematology Disease Topics & Pathways:
Research, Clinical Research, real-world evidence
Saturday, December 10, 2022: 12:15 PM

Narendranath Epperla, MD, MS1, Qiuhong Zhao, MS2*, Lauren Shea, MD3*, Reem Karmali, MD, MSc4, Pallawi Torka, MD5, Timothy Seijung Oh, MD6*, Andrea Anampa-Guzman, MD5*, Ximena Jordan Bruno, MD7, Elvira Umyarova, MD7, Kathryn Lindsey, MD8*, Irl Brian Greenwell, MD8, Sayan Mullick Chowdhury, DO, PhD9*, Yazeed Sawalha, MD10, Beth Christian11, Natalie S. Grover, MD12, Nancy L. Bartlett, MD13 and Adam J. Olszewski, MD14

1The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
2Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
3Washington University, St. Louis, MO
4Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
5Roswell Park Comprehensive Cancer Center, Buffalo, NY
6Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL
7University of Vermont, Burlington, VT
8Hollings Cancer Center, Medical University of South Carolina, Charleston, SC
9Ohio State University Medical Center, Columbus, OH
10Division of Hematology, The Ohio State University Wexner Medical Center, Columbus, OH
11The Ohio State University Comprehensive Cancer Center, Columbus, OH
12Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
13Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
14Division of Hematology/Oncology, Brown University, Providence, RI

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma that includes 3 subtypes: extranodal marginal zone lymphoma (EMZL) of the mucosa-associated lymphatic tissue (MALT), splenic MZL (SMZL), and nodal MZL (NMZL). Outside of case reports and small case series, the relevance of monoclonal protein (M-protein) in patients with MZL at diagnosis is largely unknown. Hence, we sought to evaluate the impact of M-protein at diagnosis on outcomes in patients with MZL.

This multicenter, retrospective cohort study of MZL patients treated at 8 US medical centers included patients who were ≥18 years old, diagnosed with MZL from 2010-2020, and had information on M-protein at diagnosis. Patients who were on observation or received antibiotics only were excluded. Patients were grouped according to the presence or absence of M-protein detectable by serum protein electrophoresis or immunofixation. The primary endpoint was progression-free survival (PFS). Secondary endpoints were time from diagnosis to systemic therapy, cumulative incidence of relapse in stage 1 disease after local treatment (surgery or radiation therapy), and cumulative incidence of transformation in M-protein versus no M-protein groups. PFS was defined as the time from the start of first-line therapy until lymphoma relapse/progression or death from any cause, censoring at the last clinical assessment.

Among 501 eligible patients with newly diagnosed MZL, 152 (30%) had detectable M-protein at diagnosis and 349 (70%) did not. Among those with M-protein, 59% (n=90) had IgM, 29% (n=44) had IgG, 3% (n=4) had both IgM and IgG, and 9% (n=14) had non-IgM/non-IgG M-protein and light chains. Patients in the M-protein group had a higher median age (66 vs 61 years), more advanced stage disease (76% vs 53%), lower albumin (27% vs 15%), and were more likely to receive R-chemotherapy (39% vs 23%) compared to no M-protein group.

The median PFS was 3.2 years (95%CI=2.1–5.6) in the M-protein group compared to 6.6 years (95%CI=5.4-NR) in the no M-protein group (log-rank p<0.001; Figure 1) with a 3-year and 5-year PFS rates of 51% and 44% in the M-protein gp versus 74% and 59% in the no M-protein groups. In order to determine if the M-protein was independently associated with PFS, we performed Cox regression analysis in only those who received systemic therapy at diagnosis (n=377). After adjusting for factors associated with PFS in univariate analysis (age, MZL subtype, ECOG PS, albumin level, LDH>ULN, and first-line treatment regimen), M-protein remained associated with significantly inferior PFS (HR=1.80, 95%CI=1.24-2.62, p=0.002) in the multivariable analysis. There was no difference in PFS based on the type of M-protein at diagnosis (IgM vs IgG, p=0.88).

M-protein group treated with rituximab monotherapy had significantly shorter PFS compared to no M-protein group (1.9 years versus 4.3 years, p<0.001, Figure 2), however, there was no significant difference in PFS among patients treated with bendamustine and rituximab (BR, 6.1 years versus NR, p=0.14). In the EMZL subset (n=101) treated with local therapy (surgery or radiation), PFS did not significantly differ by presence/absence of M-protein at diagnosis (p=0.53).

There was no difference in the time from diagnosis to systemic therapy initiation between the M-protein and no M-protein groups with % of patients who started treatment at 1, 3, and 5 years being 89% vs 86%, 96% vs 94%, and 99% vs 98%, respectively (p=0.21). The cumulative incidence of relapse in stage 1 disease (n=144) among the recipients of local therapy was not significantly different between the M-protein and no M-protein groups (p=0.10). The cumulative incidence of transformation was significantly higher in the M-protein group compared to no M-protein group with 3-, 5-, and 10-year rate of transformation being 5.6% vs 0.6%, 8.9% vs 1.3%, and 14% vs 1.3%, respectively (p=0.001).

In this study (to our knowledge, the largest to date) of the prognostic relevance of M-protein in MZL, we found that M-protein at diagnosis was associated with shorter PFS and a higher risk of histologic transformation. Because the PFS difference was not observed after BR, immunochemotherapy may be a preferred approach over rituximab monotherapy in this group and needs to be explored further. M-protein in stage 1 EMZL was not associated with shorter PFS after standard local therapy.

Disclosures: Epperla: Pharmacyclics: Other: Ad Board; Seattle Genetics: Other: Ad Board; BeiGene: Other: Ad Board; TG Therapeutics: Other: Ad Board; Novartis: Honoraria; Incyte: Speakers Bureau. Karmali: Kite: Consultancy, Other: Advisory Board, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Other: Advisory Board; Karyopharm: Consultancy; Morphosys/Incyte: Consultancy, Other: Advisory Board, Speakers Bureau; Eusa: Consultancy; AstraZeneca: Other: Advisory Board, Speakers Bureau; Takeda: Research Funding; Genentech/Roche: Consultancy, Other: Advisory Board; Calithera: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; BeiGene: Consultancy, Other: Advisory Board, Research Funding, Speakers Bureau. Torka: Epizyme: Consultancy; Lilly USA: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy; TG Therapeutics: Consultancy; Targeted Oncology, Physician Education Review: Honoraria. Greenwell: Kyowa Kirin: Consultancy; Stemline: Consultancy. Sawalha: Celgene/BMS: Research Funding; BeiGene: Research Funding; Epizyme: Consultancy; TG Therapeutics: Research Funding. Christian: Triphase: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Seattle Genetics: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol-Myers Squibb: Research Funding; Acerta: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Grover: ADC: Other: Advisory Board; Genentech: Research Funding; Kite: Other: Advisory Board; Novartis: Consultancy; Tessa Therapeutics: Consultancy. Bartlett: Autolus, Bristol-Meyers Squibb, Celgene, Forty Seven, Janssen, Kite Pharma, Merck, Millennium, Pharmacyclics: Research Funding; Washington University School of Medicine: Current Employment; ADC Therapeutics, Roche/Genentech, Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Olszewski: Precision Bio: Research Funding; Adaptive Biotechnologies: Research Funding; Celldex: Research Funding; Acrotech Biopharma: Research Funding; Schrodinger: Consultancy; TG Therapeutics: Consultancy, Research Funding; Genmab: Consultancy, Research Funding; Genentech: Research Funding.

*signifies non-member of ASH