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3013 Ibrutinib or Chemo-Immunotherapy As Second Line Treatment in Waldenstrom Macroglobulinaemia? a Real-Life Multicentre Study

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Combination therapy, Clinical Practice (Health Services and Quality), Chemotherapy, Diseases, Treatment Considerations, Non-Biological therapies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Francesco Autore, MD, PhD1*, Alessandra Tedeschi, MD2*, Giulia Benevolo, MD3*, Nicolò Danesin, MD4*, Diana Giannarelli, PhD5*, Rita Rizzi6*, Emanuele Cencini, MD7*, Veronica Mattiello, MD8*, Isacco Ferrarini, MD, PhD9*, Jacopo Olivieri, MD10*, Ilaria Del Giudice11*, Angela Ferrari12*, Martina Bullo13*, Bernardo Rossini14*, Marina Motta, MD15*, Dario Marino16*, Idanna Innocenti, MD, PhD17*, Luca Stirparo, MD18*, Diego Petrilli19*, Pellegrino Musto, MD20*, Veronica Peri21*, Giulia Zamprogna22*, Stefan Hohaus18*, Anna Maria Frustaci, MD23*, Francesco Piazza, MD24*, Simone Ferrero, MD25 and Luca Laurenti, MD26*

1Hematology Section, Department of Radiological and Hematological Science, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
2Department of Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
3Division of Hematology 1, Department of Biotechnology and Health Sciences, University of Torino, Torino, Italy
4Azienda Ospedale Università di Padova, Padova, Italy
5Biostatistics Unit,, b Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy, Rome, Italy
6Università di Bari "Aldo Moro," A.O.U. Consorziale Policlinico di Bari, Bari, Italy
7Division of Hematology, Azienda Ospedaliera Universitaria Senese & University of Siena, Siena, Italy
8Hematology Department, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan, Milan, Italy
9Department of Engineering for Innovation Medicine, Section of Hematology, University of Verona, Verona, ITA
10Clinica Ematologica, Centro Trapianti e Terapie Cellulari "Carlo Melzi", Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy
11Hematology, Department of Translational and Precision Medicine, Sapienza University, Roma, Italy
12Arcispedale Santa Maria Nuova, Reggio Emilia, ITA
13AO Ordine Mauriziano di Torino, SCDU Ematologia e Terapie Cellulari, Turin, ITA
14IRCCS Istituto Tumori "Giovanni Paolo II” Bari, Bari, Italy
15Hematology, ASST Spedali Civili di Brescia, Brescia, Italy
16Oncologia 1, IRCCS Istituto Oncologico Veneto, Padova, Italy
17Dipartimento di Scienze di Laboratorio ed Ematologiche, Area Ematologia, Fondazione Universitaria Policlinico Agostino Gemelli, Rome, Italy
18Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy
19Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
20Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, Department of Precision and Regenerative Medicine and  Ionian Area, "Aldo Moro" University School of Medicine, Bari, Italy, Bari, Italy
21Hematology Division I, Department of Molecular Biotechnologies and Health Sciences, University of Turin/University Hospital A.O.U. “Città della Salute e della Scienza”, Turin, Italy
22Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
23ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
24UOC Di Ematologia Azienda Ospedale Università Padova, University of Padua, Padua, Italy
25Department of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, Torino, TO, Italy
26Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Agostino Gemelli University Hospital Foundation IRCCS, Rome, Italy

In the setting of relapsed patients affected by Waldenström Macroglobulinaemia (WM) chemo-immunotherapy (CT) has been substantially substituted by BTKis. Previous trials have investigated efficacy and safety of BTKis in second line without a direct comparison to CT.

The aim of our retrospective study was to assess responses and outcomes with the treatment of BTKi or CT in second line.

We enrolled 169 WM patients relapsed in the period 2008-2022 from 15 FIL centres: 85 patients were treated with ibrutinib and 84 patients with CT; of whom 34 patients with BR (bendamustine-rituximab), 21 DRC (dexamethasone-rituximab-cyclophosphamide), 15 bortezomib-based regimens and 14 palliative regimens (i.e. alkylants).

The two cohorts of ibrutinib and CT showed similar basal clinical characteristics, prognostic factors, comorbidities and also times of retreatment between first and second line (42 vs 39 months, p=0.64).

Overall response rate (ORR) was achieved in 84.7% of patients after ibrutinib and in 69% after CT (p=0.026), ibrutinib patients showed a better progression free survival (PFS) than CT patients (4-y PFS of 67% vs 48%, p=0.0045), but we did not find statistical differences in terms of time to next treatment (TTNT) and overall survival (OS); in particular 4-y TTNT was 67% for ibrutinib and 55% for CT, 4-y OS was 78% for both. ORR for both the groups was independent from presence of treatment modifications and toxicities.

Considering the 4 different groups within the CT cohort, they showed the same characteristics except for the median age at treatment (bortezomib-based: 69 yy, BR: 70 yy, DRC: 75 yy, palliative: 83 yy; p=0.007). Non-significant difference among the 4 groups was seen in terms of ORR and PFS nor of TTNT and OS, even if we registered a better PFS for BR with a median PFS of 58.2 months, followed by bortezomib-based (PFS 53.6 mo), DRC (PFS 44.6 mo) and palliative (PFS 33.6 mo).

When comparing ibrutinib to each of the 4 CT groups, different ORR were observed in each group with Ibrutinib reporting the highest rate (84.7%; p=0.023). PFS of ibrutinib was superior to PFS of DRC, bortezomib-based and palliative regimens (p=0.028, p=0.023 and p=0.04, respectively) and it showed a trend versus PFS of BR (p=0.055). Analysis showed the significant trend (p=0.057) in terms of better PFS of ibrutinib in comparison to the other 4 curves. For TTNT and OS none difference was reported based on ibrutinib and type of CT.

No differences were noted in the two subgroups of ibrutinib patients who were treated with BR or DRC as first line therapy in terms of PFS, TTNT, OS, ORR and withdrawal or dose reduction due to toxicity.

Multivariate analysis found choice of the treatment (ibrutinib vs CT), beta2microglobulin and female gender as significant variables that favourably impact on PFS, choice of the treatment, age and female gender on TTNT, age and female gender on OS.

This large retrospective real-life study showed advantages of ibrutinib versus CT in terms of ORR and PFS, except for BR, but not in terms of TTNT and OS.

Disclosures: Autore: BeiGene, AstraZeneca, AbbVie, Janssen: Honoraria. Tedeschi: AstraZeneca, AbbVie, BeiGene, Janssen, Lilly: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Benevolo: Janssen: Honoraria; Novartis: Honoraria; GSK: Honoraria; BMS: Honoraria. Del Giudice: AstraZeneca: Other: educational and editorial projects; Jansenn: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Other: educational and editorial projects. Musto: Beigene: Consultancy, Honoraria. Hohaus: Gilead: Membership on an entity's Board of Directors or advisory committees; Lilly: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Ipsen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees. Frustaci: AbbVie, BeiGene: Other: Travel, accommodations, expenses; AbbVie, BeiGene, AstraZeneca, Janssen: Consultancy. Ferrero: Sandoz: Consultancy, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Eli Lilly: Speakers Bureau; Gilead: Research Funding, 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; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gentili: Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees. Laurenti: AstraZeneva, AbbVie, Johnson and Johnson, BeiGene, Lilly: Honoraria; AstraZeneca, AbbVie: Research Funding; AstraZeneca, AbbVie, Johnson and Johnson, BeiGene, Lilly: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH