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384 Rituximab Plus Bendamustine and Cytarabine (R-BAC) in Elderly Patients with Newly Diagnosed Mantle Cell Lymphoma: Long Term Follow-up and Mrd Results of a Phase 2 Study from the Fondazione Italiana Linfomi

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Front-line Induction Therapy and Novel Agents After Relapse
Hematology Disease Topics & Pathways:
Clinical Trials, Non-Biological, Clinical Research, Chemotherapy, Therapies
Sunday, December 12, 2021: 10:45 AM

Maria Chiara Tisi, MD1*, Luca Nassi, MD2,3*, Caterina Patti, MD4*, Michele Spina, MD5, Simone Ferrero, MD6, Monica Tani, MD7*, Barbara Botto8*, Anna Lia Molinari, MD9*, Benedetta Puccini, MD10*, Emanuele Cencini, MD11*, Alice Di Rocco12*, Claudio Chini, MD13*, Chiara Ghiggi, MD14*, Renato Zambello, MD15*, Manuela Zanni, MD16*, Roberta Sciarra, MD17*, Martina Ferrante, PhD18*, Caterina Stelitano, MD19*, Alessandro Re, MD20*, Stefano Volpetti, MD21*, Vittorio Ruggero Zilioli, MD22*, Annalisa Arcari, MD23*, Francesco Merli, MD24* and Carlo Visco, MD25*

1Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy
2Hematology, Department of translational medicine, AOU Maggiore della Carità and University of Eastern Piedmont, Novara, Italy
3Department of Hematology, Careggi Hospital and University of Florence, Florence, Italy
4Division of Hematology, A.O. Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
5Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy
6Hematology 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
7Hematology Unit, Ospedale Santa Maria delle Croci, Ravenna, Italy
8Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy
9Hematology, Ospedale degli Infermi, Rimini, Rimini, Italy
10Department of Hematology, Careggi Hospital and University of Florence, Florence, ITA
11Division of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena, Italy
12Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
13Oncology ASST-settelaghi, Varese, Italy
14Hematology unit IRCCS San Martino, Genova, ITA
15Hematology and Clinical Immunology, Department of Medicine, Azienda Ospedaliera di Padova, Padova, Italy
16Hematology, SS Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy
17Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
18Hematology Division I, Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin, Italy
19Department of Haematology, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy
20Department of Hematology, ASST Spedali Civili di Brescia, Brescia, ID, Italy
21Hematology Department, Santa Maria della Misericordia Hospital - ASUFC, Udine, Udine, Italy
22Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
23U.O. Ematologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy
24Hematology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
25Department of Medicine, Section of Hematology, University of Verona, Verona, ITA

The activity of the combination of rituximab, bendamustine, and low dose cytarabine (R-BAC) was evaluated in a phase 2 multicentre trial from the Fondazione Italiana Linfomi (FIL RBAC500) in previously untreated patients with mantle cell lymphoma (MCL) who were not eligible to stem cell transplant. Maintenance treatment was not planned after induction therapy, and no patient in the study received rituximab maintenance. Fifty-seven patients (median age 71 years, range 61-79) were recruited and treated with 4 to 6 cycles between 2012 and 2014. Despite some concern in terms of hematological toxicity, the R-BAC regimen was associated with high complete remission (CR) rate (91%), 2-years overall survival (OS) of 86% (74-93), and 2-years progression free survival (PFS) of 81% (68-89). Here, we present long-term survival outcomes.

After 7 years of median follow-up (86 months, range 57-107), the median OS and PFS for all patients were not reached (Figure 1A and 1B). The 7-years PFS and OS rates were 56% (95%CI 41-67) and 63% (95%CI 46-72), respectively. Patients who achieved CR (n=53) had a 7 years PFS of 59% (95% CI 44-71), with the curve that appears to plateau after 6 years. Adverse predictive factors affecting PFS were blastoid morphology (p<0.05), elevated Ki67 > 30% (p<0.05), and failure to achieve CR after 2 cycles (p=0.03). Early-progression of disease (<24 months from start of R-BAC) was associated with impaired overall survival (p<0.05).

Eight patients (14%) developed a secondary neoplasia: 1 parotid heteroplasia, 1 parotid nodular hyperplasia, 1 prostate cancer, 1 bladder cancer, 1 larynx, 1 thyroid cancer, 1 lung cancer and 1 secondary acute myeloid leukemia.

Among the 25 relapsed patients, 8 did not receive any other treatment. Six had Ibrutinib monotherapy as second line, of whom 4 responded (3 are still in CR), 4 had CHOP or CHOP-like regimens with only partial responses.

As per protocol, 31 patients with molecular marker at diagnosis and available samples were followed-up for minimal residual disease (MRD) with ASO-droplet digital polymerase chain reaction (D-PCR). Patients with MRD persistence at the end of induction, either in peripheral blood or bone marrow, had significantly worse 7 years-PFS (p<0.05 for them both).

In conclusion, in elderly patients with newly diagnosed MCL, R-BAC showed sustained efficacy over time, which compared favorably with any other reported immuno-chemotherapy regimen (with or without maintenance) in similar populations. With a median OS exceeding 60% after 7-years this regimen has significantly impacted on the life-expectancy of elderly patients with MCL.

Disclosures: Tisi: Incyte: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nassi: Takeda: Consultancy; Incyte: Consultancy; Kyowa Kirin: Consultancy; Roche: Consultancy. Ferrero: Gilead: Research Funding, Speakers Bureau; Morphosys: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Speakers Bureau; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Clinigen: Membership on an entity's Board of Directors or advisory committees. Zilioli: Takeda: Other: travel expenses, accommodation; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Roche, Italfarmaco: Consultancy, Honoraria; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Merli: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; EUSA Pharma: Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses.

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