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. 2024 Apr 11:72:102592.
doi: 10.1016/j.eclinm.2024.102592. eCollection 2024 Jun.

Marginal zone lymphoma international prognostic index: a unifying prognostic index for marginal zone lymphomas requiring systemic treatment

Luca Arcaini  1   2 , Côme Bommier  3   4 , Juan Pablo Alderuccio  5 , Michele Merli  6 , Nicole Fabbri  1 , Maria Elena Nizzoli  7   8 , Matthew J Maurer  4   9 , Vittoria Tarantino  10 , Simone Ferrero  11 , Sara Rattotti  2 , Annalisa Talami  8 , Roberta Murru  12 , Arushi Khurana  9 , Raphael Mwangi  4 , Marina Deodato  13 , Emanuele Cencini  14 , Francesca Re  15 , Carlo Visco  16 , Andrew L Feldman  17 , Brian K Link  18 , Marcia Torresan Delamain  19 , Michele Spina  20 , Ombretta Annibali  21 , Alessandro Pulsoni  22 , Andrés J M Ferreri  23 , Caterina Cecilia Stelitano  24 , Elsa Pennese  25 , Thomas M Habermann  9 , Luigi Marcheselli  26 , Sunwoo Han  27 , Isildinha M Reis  27   28 , Marco Paulli  1   29 , Izidore S Lossos  5 , James R Cerhan  4 , Stefano Luminari  7   30
Affiliations

Marginal zone lymphoma international prognostic index: a unifying prognostic index for marginal zone lymphomas requiring systemic treatment

Luca Arcaini et al. EClinicalMedicine. .

Abstract

Background: Marginal zone lymphomas (MZL), comprised of three unique but related subtypes, lack a unifying prognostic score applicable to all the patients in need for systemic chemotherapy and/or immunotherapy.

Methods: Patients from the prospective NF10 study (NCT02904577) with newly diagnosed MZL and receiving frontline systemic therapy at diagnosis or after observation were used to train a prognostic model. The primary endpoint was progression-free survival (PFS) from start of treatment. The model was externally validated in a pooled analysis of two independent cohorts from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource and the University of Miami.

Findings: We identified 501 eligible patients. After multivariable modeling, lactate dehydrogenase (LDH) above upper normal limit, hemoglobin <12 g/dL, absolute lymphocyte count <1 × 109/L, platelets <100 × 109/L, and MZL subtype (nodal or disseminated) were independently associated with inferior PFS. The proposed MZL International Prognostic index (MZL-IPI) combined these 5 factors, and we defined low (LRG, 0 factors, 27%), intermediate (IRG, 1-2 factors, 57%) and high (HRG, 3+ factors, 16%) risk groups with 5-y PFS of 85%, 66%, and 37%, respectively (c-Harrell = 0.64). Compared to the LRG, the IRG (Hazard Ratio [HR] = 2.30, 95% CI 1.39-3.80) and HRG (HR = 5.41, 95% CI 3.12-9.38) had inferior PFS. Applying the MZL-IPI to the pooled US cohort (N = 353), 94 (27%), 192 (54%), and 67 (19%) patients were classified as LRG, IRG, and HRG, respectively, and the model was validated for PFS (log-rank test p = 0.0018; c-Harrell = 0.578, 95% CI 0.54-0.62). The MZL-IPI was also prognostic for OS in both the training and the external validation sets.

Interpretation: MZL-IPI is a new prognostic score for use in all patients with MZL considered for systemic treatment.

Funding: The MER was supported by P50 CA97274 and U01 CA195568.

Keywords: Marginal zone lymphoma; Prognosis.

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Conflict of interest statement

LA: Grants or contracts from any entity: My First AIRC grant n. 11,415 2012–2014; Investigator Grant AIRC (2018–2022); Honoraria: EUSA Pharma, Novartis. Participation on a Data Safety Monitoring Board or Advisory Board Roche, Janssen-Cilag, Verastem, Incyte, EUSA Pharma, Celgene/Bristol Myers Squibb, Kite/Gilead, ADC Therapeutics, Novartis; Support for attending meetings and/or travel: Roche. CB: Grants or contracts from any entity: INSERM, AvieSan ITMO Cancer, LYSA/ELI: Bertrand Coiffier Prize Institut Servier; Consulting fees: Currety; Support for attending meetings and/or travel: Mayo Clinic. JPA: Grants or contracts from any entity: Lymphoma Research Foundation, US Department of Defense; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: ADC Therapeutics, Regeneron, Genentech. MM: Support for attending meetings and/or travel: Janssen. MJM: Grants or contracts from any entity: BMS, Roche, GenMab; Consulting fees: BMS; Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca. CV: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Janssen, Lilly, Novartis, Gilead, Takeda, Kyowa-Kirin, Roche, Astra Zeneca, Beigene, Gentili. BKL: Grants or contracts from any entity: Roche/Genentech, Seattle Genetics, Genmab, AstraZeneca. OA: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Janssen, Beigene, Ely Lilli, Amgen, Sanofi. AP: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Msd, Pfizer, Sandoz, Takeda, Gilead, Bms, Janssen, Beigene; Participation on a Data Safety Monitoring Board or Advisory Board: Takeda, Roche. TMH: All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): Lymphoma SPORE NCI CA 97274; Participation on a Data Safety Monitoring Board or Advisory Board: Seagen, Eli Lilly & Co. LM: Other financial or non-financial interests: Scientific consultant for Sandoz spa, 2022–2023, free of fee. JRC: All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): National Cancer Institute, Grants P50 CA97274 and U01 CA195568 (to Mayo); Grants or contracts from any entity: BMS, Genentech, and Genmab; Participation on a Data Safety Monitoring Board or Advisory Board and SMC member: Protagonist Therapeutics. SL: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Novartis, Incyte, BMS, Kite, Regeneron, Abbvie, Genmab, Sobi, Beigene; Support for attending meetings and/or travel: Roche, Beigene, Regeneron. NF, MEN, VT, SF, SR, AT, RM, AK, RM, MD, EC, FR, ALF, MDT, MS, AJMF, CS, EP, SH, IMR, ISL: no COI.

Figures

Fig. 1
Fig. 1
Progression-free survival of patients with marginal zone lymphoma according to MZL-IPI risk category (low, intermediate, high) (training sample) (A) and of patients from US Cohort (the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence, SPORE, Molecular Epidemiology Resource, MER, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA) (validation sample) (B).
Fig. 2
Fig. 2
Overall survival of patients with marginal zone lymphoma according to MZL-IPI risk category (low, intermediate, high) (training sample) (A) and of patients from US Cohort (the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence, SPORE, Molecular Epidemiology Resource, MER, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA) (validation sample) (B).
See this image and copyright information in PMC

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