IBRUTINIB COMPARED TO IMMUNO-CHEMOTHERAPY FOR CENTRAL NERVOUS SYSTEM RELAPSE OF MANTLE CELL LYMPHOMA: A REPORT FROM FONDAZIONE ITALIANA LINFOMI (FIL) AND EUROPEAN MANTLE CELL LYMPHOMA NETWORK (EMCLN)
Author(s): ,
Chiara Rusconi
Affiliations:
Hematolgy and Bone Marrow Transplantation,IRCCS Fondazione Istituto Nazionale dei Tumori,Milan,Italy
,
Chan Y. Cheah
Affiliations:
Department of Hematology, Sir Charles Gairdner Hospital,Perth,Austria
,
David Tucker
Affiliations:
Department of Haematology,Royal Cornwall NHS Trust,Truro,United Kingdom
,
Toby A. Eyre
Affiliations:
Oxford University Hospitals, NHS Foundation Trust,Oxford Cancer and Haematology Centre, Churchill Hospital,Oxford,United Kingdom
,
Pavel Klener
Affiliations:
First Faculty of Medicine,General University Hospital, Charles University in Prague,Prague,Czech Republic
,
Eva Giné
Affiliations:
Hematology Department,Hospital Clínic,Barcelona,Spain
,
Lara Crucitti
Affiliations:
Division of Hematology,ASST Grande Ospedale Metropolitano Niguarda,Milan,Italy
,
Cristina Muzi
Affiliations:
Division of Hematology,ASST Grande Ospedale Metropolitano Niguarda,Milan,Italy
,
Sophie Bernard
Affiliations:
Service d'onco-hématologie, Hôpital Saint-Louis, AP-HP,Paris,France
,
Rebecca L. Auer
Affiliations:
Centre for Haemato-Oncology,St.Bartholomew's Hospital Barts Health NHS Trust,London,United Kingdom
,
Chiara Pagani
Affiliations:
U.O. Ematologia,Spedali Civili di Brescia,Brescia,Italy
,
Wojciech Jurczak
Affiliations:
Department of Clinical Oncology,Maria Sklodowska-Curie National Institute of Oncology,Cracow,Poland
,
Heidi Mocikova
Affiliations:
Third Faculty of Medicine,University Hospital Kralovske Vinohrady, Charles University in Prague,Prague,Czech Republic
,
Hanneke C. Kluin-Nelemans
Affiliations:
University Medical Center Groningen,University of Groningen ,Groningen,Netherlands
,
Emanuele Cencini
Affiliations:
U.O.C. Ematologia,Ospedale Policlinico Santa Maria alle Scotte,Siena,Italy
,
Ana Marin-Niebla
Affiliations:
Hematology Department,Vall d'Hebron Institute of Oncology,Barcelona,Spain
,
Michael E. Williams
Affiliations:
Hematology/Oncology Division,University of Virginia Cancer Center,Charlottesville,United States
,
Piera Angelillo
Affiliations:
Lymphoma Unit Department of OncoHematology,San Raffaele Scientific Institute,Milan,Italy
,
Paolo Nicoli
Affiliations:
Ematologia,AUO San Luigi Gonzaga,Orbassano,Italy
,
Annalisa Arcari
Affiliations:
Hematology Unit,Azienda AUSL,Piacenza,Italy
,
Lucia Morello
Affiliations:
Department of Oncology and Hematology ,Humanitas Cancer Center,Milan,Italy
,
Donato Mannina
Affiliations:
UOC di Ematologia,Azienda Ospedaliera Papardo,Messina,Italy
,
Orsola Vitagliano
Affiliations:
Division of Hematology,Cardarelli Hospital,Napoli,Italy
,
Roberto Sartori
Affiliations:
Hematology Department,Castelfranco Veneto Regional Hospital, Castelfranco Veneto,Treviso,Italy
,
Annalisa Chiappella
Affiliations:
Division of Hematology,AO Città della Salute e della Scienza di Torino,Torino,Italy
,
Roberta Sciarra
Affiliations:
Division of Hematology,Fondazione IRCCS Policlinico San Matteo,Pavia,Italy
,
Piero Maria Stefani
Affiliations:
U.O.C. di Ematologia, Dipartimento di Medicina Specialistica,Locale Socio-Sanitaria della Marca Trevigiana,Treviso,Italy
,
Martin Dreyling
Affiliations:
University Hospital Munich,LMU Munich,Munich,Germany
,
John Seymour
Affiliations:
Department of Hematology,Peter MacCallum Cancer Centre & Royal Melbourne Hospital,Melbourne,Australia
Carlo Visco
Affiliations:
Department of Medicine, Section of Hematology,University of Verona,Verona,Italy
EHA Library. Rusconi C. 06/12/20; 295049; S229
Chiara Rusconi
Chiara Rusconi
Contributions
Abstract

Abstract: S229

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background

Central nervous system (CNS) relapse of Mantle Cell Lymphoma (MCL) is a rare phenomenon for which a standard of care has not been identified. Responses to conventional treatment for CNS-MCL are poor, with median survival of less than 6 months. Ibrutinib is approved for relapsed/refractory MCL, and small series demonstrated efficacy in CNS disease due to its ability of crossing the blood-brain barrier (BBB). 

Aims
To report the outcome of MCL patients (pts) with documented CNS involvement at relapse, and analyze response and survival of pts treated with ibrutinib compared to standard therapy.

Methods
We retrospectively analyzed a multi-center series of consecutive pts with CNS relapse of systemic MCL treated between 2000 and 2019 in 38 centers (20 internationals and 18 from FIL). The cohort included 39 pts receiving standard therapy as described in previous reports. Overall survival (OS) was estimated from the time of initiation of CNS-MCL directed therapy until death.

Results
Eighty-four pts were analyzed: 58 pts (69%) were treated with standard immuno-chemotherapy (CHT) (standard cohort, SC), while 26 pts (31%) were treated with ibrutinib (ibrutinib cohort, IC). The two cohorts displayed similar characteristics: median age was 62 years (yrs) (range: 38-84) in SC and 63 years (range: 48-77) in IC (p=0.26); blastoid variant was diagnosed in 29% SC and 24% IC pts (p=0.78); MIPI score was high in 63% SC and in 71% IC pts (p=0.64). Median prior therapies for MCL preceding CNS relapse was 1 (range: 1-5) in the SC and 1 (range: 1-2) in the IC (p=0.15). Median time from initial MCL diagnosis to CNS relapse was 15 months (range: 2-122) in the SC, and 19 months (range: 1-86) in the IC (p=0.45). In the SC, treatment for CNS relapse consisted of rituximab plus BBB crossing therapies in 28 pts (48%), rituximab plus bendamustine-based in 6 pts (11%), intrathecal (IT) CHT only in 17 pts (29%) and radiotherapy in 7 pts (12%). BBB crossing therapies consisted mainly of HD-methotrexate, alone in 7 pts (25%), combined with HD-Ara-C in 19 pts (68%), and 2 pts (7%) received ifosfamide-based. In the SC, IT therapy was added in 45 pts (78%). Patients in the IC received ibrutinib 560 mg p.o. daily until progression or toxicity; IT CHT was given concurrently in 12 pts (46%). Data for response assessment were available for 79 pts (89%). Overall-response rate (ORR) was 72% in the IC and 39% in the SC, while complete response (CR) rate was 42% and 17%. Considering pts receiving BBB crossing treatments within the SC, ORR was 46% and CR rate 22%. The difference between CR rate in the IC and BBB crossing therapies group was statistically significant (42% vs 22%, p=0.02). With a median follow-up of 4.3 months, the 1-y OS of the entire study population was 27%. Ibrutinib conferred a statistically significant superior 1-y OS compared to SC (61% vs 16%; HR=0.29, p < 0.001). Similarly, OS was confirmed superior with ibrutinib compared to pts receiving BBB crossing therapies (1-y rates: 59% vs 25%; HR=0.39, p=0.011) (Fig. 1). IT therapy was not of additional benefit in the IC (IT vs no IT: 1-y OS 63% vs 60%, p=0.72) or in the SC cohort (1-y OS 13% vs 25% p=0.45). In the IC no unexpected toxicity was reported, including no cases of invasive fungal infection.

Conclusion
This is the first large cohort analyzing outcome of pts treated with ibrutinib for CNS relapse of MCL. With the usual limitations of a retrospective analysis, ibrutinib was associated with an improved response and survival compared to standard immuno-CHT in this difficult to treat population, with half of pts alive at 1 year.

Session topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Keyword(s): CNS lymphoma, Ibrutinib, Mantle cell lymphoma

Abstract: S229

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background

Central nervous system (CNS) relapse of Mantle Cell Lymphoma (MCL) is a rare phenomenon for which a standard of care has not been identified. Responses to conventional treatment for CNS-MCL are poor, with median survival of less than 6 months. Ibrutinib is approved for relapsed/refractory MCL, and small series demonstrated efficacy in CNS disease due to its ability of crossing the blood-brain barrier (BBB). 

Aims
To report the outcome of MCL patients (pts) with documented CNS involvement at relapse, and analyze response and survival of pts treated with ibrutinib compared to standard therapy.

Methods
We retrospectively analyzed a multi-center series of consecutive pts with CNS relapse of systemic MCL treated between 2000 and 2019 in 38 centers (20 internationals and 18 from FIL). The cohort included 39 pts receiving standard therapy as described in previous reports. Overall survival (OS) was estimated from the time of initiation of CNS-MCL directed therapy until death.

Results
Eighty-four pts were analyzed: 58 pts (69%) were treated with standard immuno-chemotherapy (CHT) (standard cohort, SC), while 26 pts (31%) were treated with ibrutinib (ibrutinib cohort, IC). The two cohorts displayed similar characteristics: median age was 62 years (yrs) (range: 38-84) in SC and 63 years (range: 48-77) in IC (p=0.26); blastoid variant was diagnosed in 29% SC and 24% IC pts (p=0.78); MIPI score was high in 63% SC and in 71% IC pts (p=0.64). Median prior therapies for MCL preceding CNS relapse was 1 (range: 1-5) in the SC and 1 (range: 1-2) in the IC (p=0.15). Median time from initial MCL diagnosis to CNS relapse was 15 months (range: 2-122) in the SC, and 19 months (range: 1-86) in the IC (p=0.45). In the SC, treatment for CNS relapse consisted of rituximab plus BBB crossing therapies in 28 pts (48%), rituximab plus bendamustine-based in 6 pts (11%), intrathecal (IT) CHT only in 17 pts (29%) and radiotherapy in 7 pts (12%). BBB crossing therapies consisted mainly of HD-methotrexate, alone in 7 pts (25%), combined with HD-Ara-C in 19 pts (68%), and 2 pts (7%) received ifosfamide-based. In the SC, IT therapy was added in 45 pts (78%). Patients in the IC received ibrutinib 560 mg p.o. daily until progression or toxicity; IT CHT was given concurrently in 12 pts (46%). Data for response assessment were available for 79 pts (89%). Overall-response rate (ORR) was 72% in the IC and 39% in the SC, while complete response (CR) rate was 42% and 17%. Considering pts receiving BBB crossing treatments within the SC, ORR was 46% and CR rate 22%. The difference between CR rate in the IC and BBB crossing therapies group was statistically significant (42% vs 22%, p=0.02). With a median follow-up of 4.3 months, the 1-y OS of the entire study population was 27%. Ibrutinib conferred a statistically significant superior 1-y OS compared to SC (61% vs 16%; HR=0.29, p < 0.001). Similarly, OS was confirmed superior with ibrutinib compared to pts receiving BBB crossing therapies (1-y rates: 59% vs 25%; HR=0.39, p=0.011) (Fig. 1). IT therapy was not of additional benefit in the IC (IT vs no IT: 1-y OS 63% vs 60%, p=0.72) or in the SC cohort (1-y OS 13% vs 25% p=0.45). In the IC no unexpected toxicity was reported, including no cases of invasive fungal infection.

Conclusion
This is the first large cohort analyzing outcome of pts treated with ibrutinib for CNS relapse of MCL. With the usual limitations of a retrospective analysis, ibrutinib was associated with an improved response and survival compared to standard immuno-CHT in this difficult to treat population, with half of pts alive at 1 year.

Session topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Keyword(s): CNS lymphoma, Ibrutinib, Mantle cell lymphoma

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