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4406 Clinical Characteristics, Treatment Approach and Long-Term Outcomes of 678 Patients with Symptomatic Waldenstrom’s Macroglobulinemia: Comprehensive Insights from a Spanish Registry of IgM Gammapathies

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
adult, Clinical Practice (Health Services and Quality), Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Elham Askari1*, David F. Moreno2*, Fernando Escalante3*, Amalia Domingo-González4*, Angela Heredia5*, Arancha Bermúdez6*, Miguel Canales7*, Mario Arnao Herraiz8*, Maria Magdalena Alcala Peña9*, Ana Saus Carreres10*, Pablo Ríos Rull11*, María Casanova12*, Mercedes Gironella13*, Paz Ribas Garcia14*, Javier De La Rubia15*, Belén Navarro16*, María-Jesús Blanchard17*, Cristina Motlló18*, Ricarda García Sánchez19*, Francisco Taboada Alameda20*, Antonio Garcia21*, Eugenio Abella22*, Miguel Angel Alvarez Rivas23*, Joan Bargay24*, Laura Abril Sabater25*, Amanda Lopez Picado26*, Carlos Fernández de Larrea2* and Ramon Garcia-Sanz27

1Department of Hematology, Hospital Universitario Fundación Jiménez Diaz, Madrid, Spain
2Hospital Clínic de Barcelona, Barcelona, Spain
3Hospital Universitario de Leon, Leon, Spain
4Hospital Universitario Fundación Jiménez Diaz, Madrid, Spain
5Hospital Virgen de la Arrixaca, Murcia, Spain
6Hospital Marques de Valdecilla, Santander, Spain
7Clínica Universidad de Navarra Cancer Center (CCUN), Pamplona, Spain
8Hospital La Fe, Valencia, Spain
9Hospital general de Malaga, Malaga, Spain
10Hospital Clínico de Valnecia, Valencia, Spain
11Hospital Ntra. Sra. de Candelaria, Sta. Cruz De Tenerife, ESP
12Hospital Costa Del Sol Marbella, Marbella, Spain
13Hospital Universitari Vall d'Hebron, Barcelona, Spain
14Hospital Dr. Peset, Valencia, Spain
15Hospital Universitario y Politécnico La Fe, Valencia, Spain
16Hospital Universitario Puerta de Hierro, Majadahonda, Spain
17Hospital Universitario Ramón y Cajal, Madrid, Spain
18Hospital Sant Joan de Déu de Manresa, Barcelona, Spain
19Hospital Virgen de la Victoria, Malaga, Spain
20Hospital Vital Alvarez Buylla, Oviedo, Spain
21Hospital Arnau de Villanova, Lleida, Spain
22Hospital del Mar, Barcelona, Spain
23Hospital Reina Sofia, Madrid, Spain
24Hospital Universitario Son Llàtzer. IdIsBa., Palma de Mallorca, Spain
25Institut Català d’Oncologia, Badalona, Spain
26Sociedad Española de Hematologia, Madrid, Spain
27Department of Hematology, University Hospital of Salamanca, Salamanca, Spain


The pathogenesis of Waldenstrom’s macroglobulinemia (WM) involves the clonal expansion of lymphoplasmacytic B cells in bone marrow, producing monoclonal immunoglobulin M (IgM). The heterogeneity of clinical manifestations in this uncommon disease represents the treatment approach more challenging. Multicenter registries may help in improving health care and scientific research. PRAME is a Spanish national registry of WM and IgM-related disorders with comprehensive data collection, providing insights for a better understanding of WM.


This is a retrospective, multicenter study that included newly diagnosed symptomatic WM (SWM) patients, evaluated at (24) Spanish hospitals between 1990 and 2023. All patients had confirmed diagnoses of SWM according to the International Workshop Consensus. Data collection on patients' demographics and disease epidemiology, clinical characteristics, diagnosis, treatment approaches and outcomes were performed from patients' local medical files.


From 1796 total patients included in the Spanish registry for IgM gammopathies, a total of 678 newly SWM patients were identified. The median age was 71(range 35-94) years, 37% of patients had aged ≥ 75 years and 63% were male. The most common symptom at diagnosis was anemia (43%), followed by B symptoms (30%). Fifteen percent had peripheral neuropathy (PN) as the first WM symptom (39% with sensitive motor PN). Hyperviscosity was only observed in 15%. The free light chain isotypes were mostly kappa (75.4%). Less than 5% of the total cohort, had an ECOG ≥3, at diagnosis. Among 403 patients, who had samples available for assessing MYD88 L265P by quantitative allele-specific PCR, 75% were positive for the mutation. However, out of the 199 patients assessed for CXCR4(S388X) mutation, only 12% were positive. The first line of therapy was started in 98% of patients. Plasmapheresis was indicated in 10%, with a median number of 2 sessions. The most frequent indications for initiating the treatment were anemia (48%), B symptoms (13%), and neuropathy (9%). Symptoms related to IgM monoclonal and extramedullary involvement were seen in 15% (56% associated with hyperviscosity) and 11.3%, respectively. The main first-line treatment regimens received were: chlorambucil (37%), dexamethasone, rituximab and cyclophosphamide (DRC)(21%), rituximab monotherapy (13%), bendamustine/rituximab (BR) (9.1%), Bruton tyrosine kinase (BTK) inhibitors (7%), and bortezomib, dexamethasone and rituximab (BDR) (5.5%). The overall and major response rates (ORR and MRR) were 67% and 58%, respectively. (Table 1). The MRR was higher among patients who received BR as the first line of therapy (88%), with a 26% of complete response (CR) and 21% of very good partial responses (VGPR). The CR+VGPR rates with other common regimens were 17% for DRC, 9% for BDR and 21% for BTK inhibitors, respectively. With a median follow-up of 96 months (IQR, 43 to 192), the median overall survival (OS) was 8.7 years (95% confidence interval [CI]:7.3-10.1) and the median progression-free survival (PFS) was 6.8 years (95% CI:6.2-7.5) with no relevant improvement over the last years. (Figure 1)


In the current registry, we observed a high proportion of younger patients with good performance status at diagnosis. Among newly diagnosed SWM patients, BR demonstrated ongoing superiority as a front line of therapy, leading to deeper responses compared to other therapeutic schemes. There were no significant differences in OS between different times of diagnosis. This Spanish registry for SWM contributes to advancing knowledge and the continual enhancement of treatment strategies for WM.

Disclosures: Askari: GSK: Consultancy; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau. Bermúdez: Novartis: Consultancy, Speakers Bureau; Pfitzer: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Canales: Beigene: Consultancy; BMS: Consultancy; Incyte: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Kite: Consultancy; Kyowa: Consultancy; Lilly: Consultancy; Roche: Consultancy; Takeda: Consultancy; Incyte: Speakers Bureau; Janssen: Speakers Bureau; Kite: Speakers Bureau; Kyowa: Speakers Bureau; Roche: Speakers Bureau; Takeda: Speakers Bureau. Herraiz: Janssen: Consultancy, Speakers Bureau; BMS: Consultancy; Celgene: Consultancy; Sanofi: Consultancy, Speakers Bureau; Amgen: Consultancy. Casanova: Sanofi: Speakers Bureau; BeiGene: Consultancy; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; GSK: Consultancy, Speakers Bureau. Gironella: Beigene: Consultancy; GSK: Consultancy; Janssen: Consultancy, Speakers Bureau. De La Rubia: BMS: Honoraria; GSK: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pfizer: Speakers Bureau; Sanofi: Speakers Bureau; Takeda: Research Funding; Menarini: Honoraria; Oncopharm: Honoraria. Fernández de Larrea: Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding. Garcia-Sanz: Janssen: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria.

*signifies non-member of ASH