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1566 Prognostic Role of Revised International Prognostic Score for Waldenstrom Macroglobulinemia (rIPSSWM) in Newly Diagnosed Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma: A Report from the NF10 International, Prospective, Observational Study of the Fondazione Italiana Linfomi

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Lymphomas, non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Diseases, indolent lymphoma, real-world evidence, Lymphoid Malignancies, Study Population, Human
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Angela Ferrari, MD1*, Sara Rattotti2*, Simone Ferrero, MD3, Michele Merli, MD4*, Francesco Merli, MD1*, Sara Veronica Usai5*, Marina Deodato, MD6*, Alessandro Pulsoni7*, Emanuele Cencini, MD8*, Francesca Re, MD9*, Maria Chiara Tisi, MD10*, Marcia Torresan Delamain, MD, PhD11*, Michele Spina, MD12, Ombretta Annibali, MD, PhD13*, Angela Rago, MD14*, Carola Boccomini15*, Andrés J M Ferreri, MD16, Maria Elena Nizzoli, MD17*, Luca Arcaini18*, Stefano Luminari, MD19 and Marzia Varettoni, MD2*

1Hematology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
2Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
3Hematology 1 U, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy/AOU “Città della Salute e della Scienza di Torino”, Torino, Italy
4Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi, University of Insubria, Varese, Italy
5Hematology, Ospedale Oncologico Armando Businco, Cagliari, Italy
6ASST Grande Ospedale Metropolitano Niguarda, Niguarda Cancer Center, Department of Hematology, Milano, Italy
7Institute of Hematology, University La Sapienza and Hospital Umberto I, Roma, Italy
8Division of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena, Italy
9Hematology and CTMO, Azienda Ospedaliera-Universitaria di Parma, Parma, Italy
10Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy
11Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil
12Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy
13Unit of Hematology, Stem Cell Transplantation, University Campus Bio Medico, Rome, Italy
14UOSD Ematologia, ASL Roma 1, Rome, Italy
15Division of Hematology 2, AOU Città della Salute e della Scienza di Torino, Torino, Italy
16Lymphoma Unit, Dept of Onco-hematology, IRCCS San Raffaele Scientific Institute, Milano, Italy
17PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy
18Department of Molecular Medicine, University of Pavia, Pavia, Italy
19Hematology Unit, Azienda USL-IRCCS di Reggio Emilia, REGGIO EMILIA, Italy

Background: Revised international prognostic score for Waldenstrom macroglobulinemia (rIPSSWM) has been recently validated for symptomatic WM patients in need of treatment and was built on the independent prognostic role of Age, LDH, Serum Albumin and Beta2microglobulin. In 2010 the NF10 study was started by the Fondazione Italiana Linfomi as a prospective registry specifically devised for investigating the prognosis of, Indolent non follicular B-Cell Lymphomas (INFL) including small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) and marginal zone lymphomas (MZL).

Methods: We aimed to assess the prognostic role of RIPSSWM (ref) on an unselected population of treatment naïve patients with LPL/WM enrolled in the NF10 registry. Main study endpoint was Overall Survival. Secondary endpoint was treatment free survival (TFS).

Results: From July 2010 to January 2020, 1535 INFL cases were registered and 1328 validated. Three hundred and seventeen cases were LPL/WM. Median age was 69 years (range 60-76); 6% had ECOG performance status > 1, median hemoglobin concentration was 12 g/dl (IQR 10 – 13.6), median serum albumin was 4 g/dl (IQR 3.6 – 4.3); serum CM was present in 254 patients with median concentration of 1.6 g/dl (IQR 0.74 – 2.4). Lactate dehydrogenase and b2-microglobulin were elevated in 21% and 59% of cases, respectively.

Overall, 191 patient received systemic therapy. Immediate systemic therapy was planned in 133 (42%) patients. Additionally 58 patients required systemic treatment due to progressive disease from watch and wait. Median time to treatment for WW patients was 18 months (95% CI 15 to 28). When systemic therapy was prescribed rituximab (R) was used in 82% and was combined with cytotoxic therapy in 76% of cases. Regarding immunochemotherapy regimens, R was combined with bendamustine in 34%, alkylating agents in 30%, fludarabine in 8%, and CHOP like in 4%.

With 58 months of median follow up (1 – 114), 5-year overall survival (OS) was 83% (95%CI: 78-88). In univariate analysis of OS, Age (>75years), elevated LDH, elevated B2M, and low serum albumin (<3.5) were associated with a different risk of death; the initial choice of deferring therapy did not impact on OS. Revised IPSSWM score could be calculated for 228 patients: 34(15%), 55(24%), 63(28%), 60(26%), and 16(7%) patients had 0,1,2,3, or 4-5 risk factors, respectively. Five-year OS was 100%, 98%, 79%, 83%, and 29% by risk group (p<0.001; c-Harrel 0.792: Figure1). The risk of dying due to lymphoma progression or due to other causes was similarly low for low risk patients (0-1 risk factors). Intermediate (2-3 RF) and high risk patients (4-5 RF) had a three-fold higher risk of dying due to causes unrelated to lymphoma compared to lymphoma related deaths. rIPSSWM was also correlated with a different TFS among patients initially observed (Figure 1: median TFS not reached for 0 RF, vs 15 months for 1-3 RF, vs 1.5 months for 4-5 RF p <0.001).

Conclusions: We were able to validate the prognostic role of rIPSSWM in an unselected population of newly diagnosed patients with LPL/WM thus extending the usefulness of this score to asymptomatic patients. The rIPSSWM was particularly able to identify a small group of patients at very high risk of death within few months from the diagnosis. Moreover the rIPSSWM was also able to predict the time to initial treatment for patients who were initially observed. The NF10 study confirms that a web-based world-wide cooperation allows the collection of a relevant and complete data set, providing a platform for future prognostic and pathobiological studies.

Disclosures: Ferrero: Incyte: Membership on an entity's Board of Directors or advisory committees; Morphosys: Research Funding; Gilead: Research Funding; Gentili: Speakers Bureau; Clinigen: 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; Jannsen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Honoraria, Speakers Bureau. Ferreri: Ospedale San Raffaele srl: Patents & Royalties: NGR-hTNAF/RCHOP in relapsed/refractory PCNSL; SNGR-hTNF in brain tumours; Adienne: Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; PletixaPharm: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Genmab: Research Funding; ADC Therapeutics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Amgen: Research Funding; Pharmacyclics: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hutchison Medipharma: Research Funding; Beigene: Research Funding. Arcaini: ADC Therapeutics: 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; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees. Luminari: GENMAB: Membership on an entity's Board of Directors or advisory committees; TAKEDA: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees; Jannsen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Regeneron: Membership on an entity's Board of Directors or advisory committees. Varettoni: ABBVIE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; ASTRAZENECA: Membership on an entity's Board of Directors or advisory committees; BEIGENE: Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; JANNSEN: Membership on an entity's Board of Directors or advisory committees, Other: travel expenses.

*signifies non-member of ASH