VITTORIO DEL FABRO ¹ Uros Markovic ¹ Sara Frazzetto ^1,2* Roberta Sciortino ³ Claudia Bellofiore ³ Mary Ann Di Giorgio ³ Valerio Leotta ³ Anna Bulla ¹ Angelo Curto Pelle ¹ Donato Mannina ⁴ Ugo Consoli ³ Mineo Giuseppe ⁵ Federica Elia ¹ Cesarina Giallongo ^1,2 Alessandra Romano ^1,2 Francesco Di Raimondo ^1,2 Concetta Conticello ¹

• ¹ Division of Hematology, Gaspare Rodolico Hospital, Catania, Sicily, Italy
• ² Postgraduate School of Hematology, University of Catania, Catania, Italy
• ³ U.O.C. Ematologia, ARNAS Garibaldi, Catania, Italy
• ⁴ Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte, Messina, Italy
• ⁵ San Vincenzo Hospital, Taormina, Italy

Background: Waldenström macroglobulinemia (WM) is a rare and indolent B-cell lymphoproliferative disorder with greater incidence in elderly patients where a precise algorithm of initial therapy is still not clear. Immunochemotherapy regimen consisting of dexamethasone, rituximab, and oral cyclophosphamide (DRC) is considered a suitable first line treatment because of its safety, efficacy and manageability. Patients and Methods: We retrospectively describe results of 36 consecutive treatment-naïve WM patients that were treated from June 2013 until June 2021 with DRC regimen every four weeks instead of three weeks, for 6 cycles. The median age was 69 years (range 42-85 years), with one third having more than 75 years. Most patients had features of advanced disease, with nearly 60% being high risk. Median IgM level prior to treatment initiation was 2.9 g/dL. Results: Overall response rate was 80% after a median time of two cycles, with 67% of patients achieving at least partial response. After a median follow-up of 59 months, the median overall survival (OS) was not reached and the median time to next treatment (TTNT) was 48 months (95% CI 25-87 months). Around 70% of the evaluable study population had 3-year survival without additional treatment, while 75% had 3-year OS rate. The treatment was well-tolerated with only two patients (6%) that recorded grade 3 pneumonia and no grade 3 hematological toxicity maybe due to regular use of growth factors for red and white blood cells. Baseline albumin level and achievement of at least minimal or partial response had significant impact on TTNT, while baseline haemoglobin and IgA level affected outcome in terms of OS (p<0.05). Conclusion: This is the first real-life experience describing the use of DRC regimen in treatment-naive WM patients with administration of therapy every 4 weeks instead of 3 weeks showing apparent comparable efficacy, along with good tolerability and safety, especially in terms of haematological toxicity, independently from comorbidity burden.