Splenic Marginal Zone Lymphoma: French Registries Population-Based Treatment and Survival Analyses (2002-2014)
Authors: Maynadie Marc , Gauthier Sophie , Mounier Morgane , Bommier Côme , Orazio Sebastien , Rachou Hélène , Monnereau Alain , Troussard Xavier , Thieblemont Catherine 
Published: November 2020

Background. Splenic Marginal Zone Lymphoma (SMZL) is a rare indolent B-cell lymphoma characterized by a massive splenomegaly and a moderate lymphocytosis. There is no standard of care for SMZL so far. The treatment is indicated if constitutional symptoms, massive splenomegaly and/or cytopenia, after a watch and wait period that is highly variable. Rituximab with or without chemotherapy, chemotherapy, and splenectomy are valid treatment approaches. Our objectives were to describe the characteristics of the patients with SMZL retrospectively collected from a French population database, to analyze the treatments received in first line (Tt1) and in second line (Tt2) in term of efficacy, and to describe their outcome.
Methods. We extracted the patients with a diagnostic of SMZL from the 3 French specialized registries databases (Basse-Normandie, Gironde and Côte d'Or; 3,6 M inhabitants) according to ICD-O-3 classification, cases coded as 9689/3 included between 2002 and 2014, with a follow-up until January 1rst, 2018. Demographic and clinical variables including clinical presentation, morphology and treatments at the first line and the second line were collected and reviewed by hematological experts in lymphoma (CT,XT,MM). World population standardized (WSP) incidence rate, observed survival (OS), net survival (NS: disease specific survival) were estimated using STATA v15.
Results. 284 patients met inclusion criteria. The WSP incidence rate was 0.30/100,000 p-y. Clinical characteristics were: median age of 72-y-old (31 - 93), male (n=148, 52%), Ann-Arbor Stage I-II (n=40, 15%), Stage IV (n= 230, 81 %), first malignancy (n=47, 17%), Hb &lt; 8g/dL (n=15, 5%), Plaq &lt; 80 G/L (n=38, 13%). A clonal B-cells blood involvement was present in 96% of cases with a RHM score of 0-2 in 84%. With a median follow-up at 7 years, the 5-year OS and NS were respectively 65% (59-70) and 74% (67-82).
Among 283 pts with Tt1 information, 232 were actively treated (82%). In Tt1, a splenectomy alone was performed in 93 cases (40%); rituximab was used alone in 12 cases (5); 39 (17%) received chemotherapy alone and 65 (28%) a combination R-chemotherapy. 61% of patients were treated within 3 months from diagnosis, others had a 17 months median delay. A CR after Tt1 was obtained in 71 cases (31%), a partial response or stable disease were found in 86 cases (37%). Relapse or progression were observed in 32 cases (20%). The median TTNT was 29 months (m); being quite equivalent in patients treated with other treatment than in patients with splenectomy alone (17.3 m vs 16.4 m, p = 0.1). Among 221 cases with Tt2 information, 57 were actively treated (25%). A splenectomy alone was performed in 3 cases (5%); rituximab was used alone in 5 cases (9%); 7 (12%) received chemotherapy alone and 40 (70%) had R-Chemotherapy. A CR was obtained in 25 cases (44%), a PR or stable disease was found in 17 cases (30%). Relapse or progression were observed in 7 cases (17%). The median TTNT was 13 m. Transformation in diffuse large B-cell lymphoma was observed in 21 cases (1 in untreated patient, 16 after Tt1 and 4 afterTt2). The 5-y NS was significantly better in patients treated by splenectomy alone than in other patients (91% vs 72%, p=0.002).
Conclusion: This study reports the real world data of SMZL from cancer registries over 12 years with a long follow-up. New drugs and strategies are in need to improve the results of conservative approaches in SMZL.

Disclosures
Thieblemont: Cellectis: Speakers Bureau; Roche, Amgen, Kyte Gilead, Celgene, Abbvie, Novartis, Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche, Hospita: Research Funding.

OffLabel Disclosure:
Rituximab used in treated patients