MCL-247: Durable Response of a Patient with a Mantle Cell Lymphoma Central Nervous System (CNS) Relapse to Treatment with a Bruton Tyrosine Kinase Inhibitor (BTKi) Monotherapy

Abstract

MCL accounts for 5% of all non-Hodgkin lymphomas. CNS involvement occurs in 4% of patients with 4 months of median survival. CNS lymphoma treatment usually involves high-dose chemotherapy + radiotherapy. BTKis block the B-cell antigen receptor signaling with decreased proliferation of malignant B-cells and promoting apoptosis. Monotherapy with BTKis is active in relapsed and refractory MCL with an ORR of 68%. BTK inhibitors may be actively transported across the blood-brain barrier or may rely on simple diffusion. We report here a durable response to BTKi monotherapy of a patient with MCL CNS relapse. Clinical case: A 57-year-old patient with MCL IVA was diagnosed on 6/15/2015. He was treated with bendamustine-rituximab and rituximab maintenance therapy. After five years in complete remission, he was admitted on March 12, 2019, with an acute organic brain syndrome. Brain MRI revealed leptomeningeal disease and CSF + for CNS involvement by MCL. He was started on steroids and ibrutinib 560 mg a day. He experienced significant improvement in Discussion: As far as we know there have been only three other patients reported in Europe with MCL CNS relapse treated with ibrutinib, a BTK inhibitor, and achieving durable responses. In our patient, the switch to a different BTK inhibitor has not affected the quality of his response. The treatment of MCL CNS relapses with a BTK inhibitor monotherapy constitutes a significant advance over high-dose chemotherapy and radiotherapy.