ABSTRACT
BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.
Subject(s)
Central Nervous System Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Lymphoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Retinal Neoplasms/drug therapy , Salvage Therapy , Adenine/analogs & derivatives , Aged , Aged, 80 and over , Central Nervous System Neoplasms/pathology , Female , Follow-Up Studies , Humans , Lymphoma/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Piperidines , Prognosis , Prospective Studies , Retinal Neoplasms/pathology , Survival RateABSTRACT
INTRODUCTION: Retinal artery occlusions (RAO) are severe conditions threatening vision, affecting the subsequent mortality of these patients. PATIENTS AND METHODS: We retrospectively reviewed the work-up performed in all patients diagnosed with retinal artery occlusions evaluated in two university hospitals in France (Tours and Angers). RESULTS: A total of 131 patients (131 eyes) with RAO were included, with a mean age of 69.5years and male predominance (64 %). Central retinal artery occlusion (CRAO) resulted in poor initial visual acuity (90 % less than count fingers), whereas those with branch retinal artery occlusion (BRAO) had better visual acuity (63.6 % better than 20/40). Systemic arterial hypertension (HTN) was the most common associated risk factor. Carotid stenosis was found in 50 % of cases, leading to endarterectomy in nine patients (6.9 %), while an underlying cardiac cause was implicated in 14 % of cases. Giant cell arteritis was diagnosed in five patients (3.8 %). DISCUSSION: Work-up of RAO may detect treatable cardiovascular and systemic conditions, allowing prevention of further ocular recurrence or stroke. CONCLUSION: Etiologic work-up of retinal arterial occlusion can diagnose potentially treatable underlying systemic conditions, such as giant cell arteritis, cardiac conditions and extracranial cerebrovascular disease. Giant cell arteritis has to be ruled out at the acute phase, while the role and timing of semi-urgent testing (supra-aortic Doppler echography, echocardiography, electrocardiography, lab work-up) or delayed testing (transesophageal echocardiography, brain imaging) have yet to be determined.
