Retrospective-prospective Study to Evaluate Treatment Management and Outcomes of Patients With Waldenström's Macroglobulinemia (WM) Treated in Italy According to the Zanubrutinib (Brukinsa®) Compassionate Use Program (CUP) and in Common Practice Following Commercial Approval.

Retrospective-prospective Study to Evaluate Treatment Management and Outcomes of Patients With Waldenström's Macroglobulinemia (WM) Treated in Italy According to the Zanubrutinib (Brukinsa®) Compassionate Use Program (CUP) and in Common Practice Following Commercial Approval

This is a non-interventional, observational, retrospective and prospective multicenter Italian study, to describe treatment management and outcomes of Waldenström's Macroglobulinemia (WM) patients treated according to the Italian Compassionate Use Program (CUP) and receiving zanubrutinib following its commercial approval.

Study Overview

• Status: Active, not recruiting
• Conditions: Waldenström's Macroglobulinemia (WM)
• Intervention / Treatment: Drug: Zanubrutinib

• Study Type: Observational
• Enrollment (Actual): 212

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy
    • A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C.D.U. Ematologia
  • Ancona, Italy
    • A.O.U. Ospedali Riuniti - Clinica di Ematologia
  • Ascoli Piceno, Italy
    • Ospedale C. e G. Mazzoni - U.O.C. di Ematologia
  • Bari, Italy
    • AOU Policlinico Consorziale - U.O. Ematologia con Trapianto
  • Biella, Italy
    • Nuovo Ospedale degli Infermi - SSD Ematologia
  • Bologna, Italy
    • Policlinico S. Orsola-Malpighi - Istituto di Ematologia "Seragnoli"
  • Bolzano, Italy
    • Ospedale Centrale di Bolzano - Divisione di Ematologia e T.M.O.
  • Catania, Italy
    • Azienda Ospedaliera Universitaria Policlinico - S. Marco - UOC di Ematologia
  • Ferrara, Italy
    • Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna - Ematologia e fisiopatologia della coagulazione
  • Florence, Italy
    • Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
  • Genova, Italy
    • Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia - Ematologia e terapie cellulari
  • Milan, Italy
    • Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda - Ematologia
  • Milan, Italy
    • ASST Grande Ospedale Metropolitano Niguarda - S.C. Ematologia
  • Milan, Italy
    • IEO Istituto Europeo di Oncologia - Divisione Ematoncologia
  • Novara, Italy
    • AOU Maggiore della Carità di Novara - SCDU Ematologia
  • Padua, Italy
    • AOU di Padova - Ematologia
  • Palermo, Italy
    • A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
  • Pavia, Italy
    • RCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
  • Pescara, Italy
    • P.O. Spirito Santo di Pescara - UOC Ematologia Dipartimento Oncologico Ematologico - ASL Pescara
  • Pisa, Italy
    • AOU Pisana - U.O. Ematologia
  • Ravenna, Italy
    • Ospedale delle Croci - Ematologia
  • Reggio Emilia, Italy
    • Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
  • Roma, Italy
    • Università Cattolica Sacro Cuore - Ematologia
  • Siena, Italy
    • AOU Senese - U.O.C. Ematologia
  • Teramo, Italy
    • Ospedale "G. Mazzini" - UOS Ematologia
  • Torino, Italy
    • A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria
  • Torino, Italy
    • A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia
  • Udine, Italy
    • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Waldenström's Macroglobulinemia (WM) treated in Italy according to the Zanubrutinib (Brukinsa®) compassionate use program (CUP) and in common practice following commercial approval.

Description

Inclusion Criteria:

• Signed and dated informed consent form
• Waldenström's macroglobulinemia diagnosis in need of treatment according to ESMO (European Society for Medical Oncology) guideline 2018
• Patients who received Zanubrutinib according to the Italian CUP or in common practice following Zanubrutinib commercial approval
• Treatment with zanubrutinib according to current SmPC (Summary of Product Characteristics)
• Treatment decision before inclusion into this non-interventional study
• Age ≥18 years

Exclusion Criteria:

• Contraindications according to SmPC for patients with WM
• Participation in an interventional clinical trial during zanubrutinib treatment
• Patients with disease progression during a BTKi treatment (if pre-treated with BTK, only those intolerants are considered eligible)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective cohort; All patients with Waldenström's macroglobulinemia enrolled in Pre-Reimbursement Access Program (PRAP) of Zanubrutinib, as per Compassionate Use Program (CUP) of Zanubrutinib, and patients treated with commercial drug (Brukinsa®) from PRAP closure to the study start.
Prospective cohort; Patients with Waldenström's macroglobulinemia treated with Zanubrutinibin clinical practice enrolled from the study start up to 12 months.	Drug: Zanubrutinib; Patients will be treated with Zanubrutinib as per routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of treatment discontinuation due to toxicity	Cumulative incidence of treatment discontinuation due to toxicity	From the date of first zanubrutinib administration to the date of definitive treatment discontinuation or dose reduction for any cause or death from any cause, from october 2020 up to 24 months since study start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)	Incidence of adverse events (AEs)	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events related to zanubrutinib.	Incidence of adverse events related to zanubrutinib.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of relevant adverse events.	Incidence of relevant adverse events.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of serious adverse events (SAEs).	Incidence of serious adverse events (SAEs).	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to death.	Incidence of adverse events leading to death.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to treatment discontinuation.	Incidence of adverse events leading to treatment discontinuation.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to dose reduction/interruption.	Incidence of adverse events leading to dose reduction/interruption.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Time to first onset of relevant adverse event.	Time to first onset of relevant adverse event.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
AEs ≥ G3 Hematological and non-hematological.	AEs ≥ G3 Hematological and non-hematological.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Impact of patients' characteristics and comorbidities on G3 or higher AEs and relevant adverse events development.	Impact of patients' characteristics and comorbidities on G3 or higher AEs and relevant adverse events development.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Frequency of transformation of WM to an aggressive lymphoma and frequency of secondary malignancies.	Frequency of transformation of WM to an aggressive lymphoma and frequency of secondary malignancies.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Major response rate (MRR)	Major response rate (MRR) (≥PR) (best reported response).	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Overall response rate (ORR)	Overall response rate (ORR, defined as MRR plus minor response rate)	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Best response	Best response (best reported response).	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Progression-free survival (PFS)	Progression-free survival (PFS) including 6, 12, and 24-month PFS rate	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Overall survival (OS)	Overall survival (OS) including 6, 12, and 24-month OS rate.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Time to treatment failure	Time to treatment failure (any treatment definitive discontinuation, incl. patient or investigator decision, toxicity, progression or death).	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Duration of response (DOR)	Duration of response (DOR)	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Change of IgM levels until end of zanubrutinib treatment.	Change of IgM levels until end of zanubrutinib treatment.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Impact of patients and disease characteristics, and biomarker test results (MYD88 and CXCR4, if available) on treatment response.	Impact of patients and disease characteristics, and biomarker test results (MYD88 and CXCR4, if available) on treatment response.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Hospital stays	Hospital stays comprises all planned and unplanned hospitalizations as well as emergency unit visits, regardless of whether there is an association with WM or not. All hospitalizations and emergency unit visits that started during therapy with zanubrutinib will be considered for hospital stays.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
EORTC-QLQ-C30	Quality of life (QoL) assessed with EORTC-QLQ-C30 questionnaire	Prospective cohort: up to 24 months (duration of study)
EQ-5D-5L	Quality of life (QoL) assessed with EQ-5D-5L questionnaire	Prospective cohort: up to 24 months (duration of study)

Collaborators and Investigators

• Sponsor: Fondazione Italiana Linfomi - ETS
• Investigators: Principal Investigator: Anna Maria Frustaci, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 28, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: December 31, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Waldenstrom Macroglobulinemia; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib
• Other Study ID Numbers: FIL_BRUCE-ITA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No