title: Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse.
abstract: The risk of central nervous system (CNS) dissemination in mantle cell lymphoma (MCL) is low and occurs late in the course of the disease. However, prognosis in such cases remains extremely poor despite high-dose antimetabolite chemotherapy. Among novel drugs used to treat relapsing MCL patients, ibrutinib, an oral inhibitor of Bruton tyrosine kinase, shows great promise. Here we report the clinical observation of 3 MCL patients with symptomatic CNS relapse treated with single-agent ibrutinib. All 3 patients had dramatic and rapid responses with almost immediate recovery from symptoms. We also confirmed that ibrutinib crosses the blood-brain barrier with parallel pharmacokinetic analyses in plasma and cerebrospinal fluid using a validated LC-MS/MS method. All responses were ongoing after 2 months to 1 year of follow-up.
authors.affiliation: Hemato-oncology Department, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Paris, France; Paris Diderot Université, Sorbonne Paris Cité, Paris, France;
authors.forename: Sophie
authors.initials: S
authors.lastname: Bernard
authors.affiliation: Pharmacology Department, APHP, Hôpital Saint-Louis, Paris, France;
authors.forename: Lauriane
authors.initials: L
authors.lastname: Goldwirt
authors.affiliation: Hemato-oncology Department, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Paris, France; Paris Diderot Université, Sorbonne Paris Cité, Paris, France;
authors.forename: Sandy
authors.initials: S
authors.lastname: Amorim
authors.affiliation: Hemato-oncology Department, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Paris, France;
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.affiliation: Pathology Department, APHP, Hôpital Saint-Louis, Paris, France;
authors.forename: Josette
authors.initials: J
authors.lastname: Brière
authors.affiliation: Radiology Department, APHP, Hôpital Saint-Louis, Paris, France;
authors.forename: Eric
authors.initials: E
authors.lastname: de Kerviler
authors.affiliation: Paris Diderot Université, Sorbonne Paris Cité, Paris, France; INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France; and Pharmacology-Genetics Laboratory, APHP, Hôpital Saint-Louis, Paris, France.
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
authors.affiliation: Pharmacology Department, APHP, Hôpital Saint-Louis, Paris, France;
authors.forename: Hélène
authors.initials: H
authors.lastname: Sauvageon
authors.affiliation: Hemato-oncology Department, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Paris, France; Paris Diderot Université, Sorbonne Paris Cité, Paris, France;
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine