Ibrutinib monotherapy in relapsed/refractory CNS lymphoma: A retrospective case series

Chamoun, Kamal; Choquet, Sylvain; Boyle, Eileen M.; Houillier, Caroline; Larrieu‐Ciron, Delphine; Jijakli, Ahmad Al; Delrieu, Vanessa; Delwail, Vincent; Morschhauser, Franck; Hoang-Xuân, Khê; Soussain, Carole

doi:10.1212/wnl.0000000000003420

Cited by 71 publications

(59 citation statements)

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“…Moreover, despite remaining acceptable, toxicity, and particularly hematological toxicity, was notably increased in the (R)-MPV-AAA regimen. Improvement of the treatment of the elderly patients might occur with new efficient agents, such as lenalidomide or ibrutinib [13,14], combined with high dose MTXbased chemotherapy. Maintenance chemotherapy to prolong remission may also be a promising approach.…”

Section: Discussionmentioning

confidence: 99%

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study

et al. 2017

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Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m D1-2). Addition of rituximab (375 mg/m D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.

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Section: Discussionmentioning

confidence: 99%

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study

et al. 2017

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“…Mounting data have suggested clinical efficacy of the oral Bruton Tyrosine Kinase (BTK) inhibitor, ibrutinib, in patients with CLL and mantle cell lymphoma involving the CNS, as well as in patients with primary CNS lymphoma (Bernard et al , ; Chamoun et al , ; Wanquet et al , ). Ibrutinib was also shown to be effective in BNS patients, based on early reports (Cabannes‐Hamy et al , ; Castillo et al , ).…”

Section: How Do We Treat Bns?mentioning

confidence: 99%

How we manage Bing–Neel syndrome

Castillo

Treon

2019

Br J Haematol

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Summary Bing–Neel syndrome (BNS) is an uncommon presentation of Waldenström macroglobulinaemia (WM), seen during the course of the disease in about 1% of patients. BNS occurs when WM cells gain access to the central nervous system (CNS) causing neurological deficits. The diagnosis of BNS is suggested by the presence of radiological abnormalities, such as leptomeningeal enhancement on magnetic resonance imaging and confirmed by the presence of clonal lymphoplasmacytic cells and MYD88 L265P in the cerebrospinal fluid. The treatment of BNS requires agents with good penetration into the CNS, such as fludarabine, methotrexate and cytarabine. The novel Bruton Tyrosine Kinase inhibitor ibrutinib has shown CNS‐penetrating properties, and recent data suggest a therapeutic role in BNS. In this review, we will discuss the clinical and pathological features, diagnostic criteria, treatment options and outcomes of patients with BNS.

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“…Thereafter, an increasing number of reports of IFD and other opportunistic infections during ibrutinib treatment have been published, with Aspergillus species, being the most frequent pathogens . Epidemiological data concerning fungal infections in patients with lymphoproliferative disorders are scarce and are mainly based on the Italian SEIFEM‐2004 study which reported an annual incidence of invasive moulds and yeast infections of 0.4% and 0.1%, respectively, for CLL and 0.9% and 0.7%, respectively, for NHL…”

Section: Introductionmentioning

confidence: 99%

Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study

Ruchlemer

Ben‐Ami

Bar-Meir

et al. 2019

Mycoses

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Summary Background Invasive fungal diseases (IFD) are life‐threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. Objectives Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. Methods Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non‐Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. Result Thirty‐five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1‐540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. Conclusions The prevalence of IFD among chronic lymphocytic leukaemia/non‐Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib‐associated IFD.

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Ibrutinib monotherapy in relapsed/refractory CNS lymphoma: A retrospective case series

Cited by 71 publications

References 6 publications

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study

How we manage Bing–Neel syndrome

Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study

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