Survival after First Relapse in Marginal Zone Lymphomas: Prospective Data from the International Observational NF10 Study By the Fondazione Italiana Linfomi

Background: Marginal Zone Lymphomas (MZL) include Splenic (SMZL), Nodal (NMZL), and Extranodal (ENMZL) pathologic subtypes and are typically associated with an indolent clinical course. Even if outcomes of most MZL cases are excellent, a significant proportion of patients relapse after first line therapy showing heterogenous behavior, with few studies describing outcomes after first relapse. In this report we investigated clinical characteristics and survival of MZL patients prospectively enrolled in the NF10 observational study who experienced a first relapse after induction systemic therapy.

Methods: The NF10 Project was started in 2010 by Fondazione Italiana Linfomi (FIL) as a prospective registry specifically conceived to investigate the prognosis of Indolent Non-Follicular B-Cell Lymphomas (INFL). All pts with a histologic confirmed diagnosis of INFL were eligible for NF10 study with no exclusion criteria. In addition to conventional MZL subtypes the category of disseminated MZL (dissMZL) was defined for cases with undefined presentation. For the current study we selected only patients who experienced a first relapse after systemic therapy. Pts were followed and treated based on local institution guidelines. Primary endpoint was Progression free survival from first relapse (PFS2) which was defined as the time from the date of first relapse (Index date) from subsequent progression, re-treatment, or death due to any cause: secondary endpoint was Survival after relapse (SAR) which was calculated from the index date to death.

Results: Between July 2010 and July 2018, 740 MZL cases had been registered by 65 centres in Europe and South America. Systemic therapy was administered to 435 patients (pts) at time of diagnosis and to 66 cases after initial watch& wait. Overall, 122 patients were identified who had a first relapse after systemic therapy and represented the study population. At index date 51% were older than 70 years (yrs), 47% were male, 36% 15% 29%, and 20% were SMZL, NMZL, ENMZL and dissMZL, respectively. LDH was elevated in 45%, MZL-IPI (Arcaini et al. 2024) was Low, Intermediate (int) and High in 14%, 57% and 29% respectively. For 57% of cases time form initial diagnosis to first relapse was shorter than 24 months (POD24). Regarding second line therapy rituximab was used in 82% of cases, mainly in combination regimens, and ASCT was used in 14% of cases. With a median follow up of 31 months (1 to 84), median PFS2 was 24 months (95% CI 14 - 54) and 2-year PFS2 rate was 49% (95%CI 39- 58). In univariate analysis a shorted PFS2 was anticipated by older age (>70 yrs), POD24, and by intermediate or high risk MZL-IPI (int vs low HR 3.21 95%IC 0.98 - 10.5); High vs low HR 6.58 95%CI 1.97 - 21.9). Among MZL subtypes both SMZL and dissMZL were associated with lower PFS rates vs ENMZL. Median SAR was not achieved and 2-y SAR rate was 64% (95% CI 54-73). In univariate analysis a shorter SAR was anticipated by older age (> 70 yrs), high risk MZL-IPI, POD24, and SMZL and dissMZL subtypes. Both PFS2 and SAR were not modified by an initial period of WW before first line therapy.

Conclusions: With this NF10 sub-study we provide prospective data about survival after first relapse in MZL and confirm the role of known prognostic factors for MZL to predict survival also in the relapsed setting, including the new MZL-IPI prognostic model. Larger collaboration studies are warranted to further analyse the outcome of relapsed MZL patients.

Luminari:BeiGene: Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Ferrero:Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Speakers Bureau; Eli Lilly: Speakers Bureau; Gentili: Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Murru:Abbvie, AstraZeneca, Beigene, Janssen: Honoraria. Stelitano:Roche, Novartis, Sandoz,Morphosys, Takeda, Octapharma, Celgene: Other: Investigartor of clinical trials. Arcaini:Kile/Gilead: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees.